WO 2012/135397 A2 4 October 2012 (04.10.2012) P O P C T

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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization II International Bureau (10) International Publication Number (43) International Publication Date WO 2012/135397 A2 4 October 2012 (04.10.2012) P O P C T

(51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, C12Q 1/68 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) International Application Number: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, PCT/US20 12/03 1047 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 29 March 2012 (29.03.2012) OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (25) Filing Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/468,700 29 March 201 1 (29.03.201 1) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/468,710 29 March 201 1 (29.03.201 1) US UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (72) Inventors; and DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (71) Applicants : LISANTI, Michael, P. [US/US]; 1104 Rod LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, man Street, Philadelphia, PA 19147 (US). SOTGIA, Fed- SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, erica [US/US]; 1104 Rodman Street, Philadelphia, PA GW, ML, MR, NE, SN, TD, TG). 19147 (US). Published: (74) Agents: UDAL, Robert, P. et al; Morgan, Lewis & — without international search report and to be republished Bockius LLP, 1701 Market Street, Philadelphia, PA upon receipt of that report (Rule 48.2(g)) 19103-2921 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM,

< | (54) Title: LACTATE-AND KETONES-INDUCED GENE SIGNATURES AND USE THE SAME FOR DIAGNOSING DISEASE AND PREDICTING CLINICAL OUTCOME Λ (57) Abstract: The present invention, at least in part, is directed to a method for discovering a biological marker (biomarker) of any 2 cancer whose growth may be modulated by mitochondrial oxidative metabolism. In certain embodiments, the method comprises (a) —- contacting a set of at least one or more metabolites (e.g., 3-hydroxybutyrate or lactate or acetoacetate or oxaloacetate or citrate or a- ketoglutarate or glutamine or combinations thereof) to a first sample of a cancer cell line, a test cancer cell line; (b) assessing a level of gene expression pattern in the test cancer cell line; and (c) comparing the level of gene expression pattern of the test cancer cell line with a level of gene expression pattern in a second sample of the same cancer cell line not treated with the set of one or more metabolites, a control cancer cell line, whereby a difference between the level of the gene expression pattern in the test cancer cell line and the level of gene expression pattern in the control cancer cell line is a biomarker indicating mitochondrial oxidative meta - bolism in the cancer represented by the cancer cell. LACTATE- AND KETONES-INDUCED GENE SIGNATURES AND USE OF THE SAME FOR DIAGNOSING DISEASE AND PREDICTING CLINICAL OUTCOME

FIELD OF THE INVENTION

[0100] This invention relates to the fields of oncology and medicine. More specifically, the invention provides biomarkers and methods of use thereof which aid the clinician in identifying those patients most likely to benefit from certain treatment regimens. The markers disclosed herein are also useful in assays to identify therapeutic agents useful for the treatment of malignancy.

BACKGROUND OF THE INVENTION

[0101] The pharmaceutical industry spends billions worldwide on research and development of new drugs, but only a handful, 5 to 10%, of drugs entering the clinical phase of drug development get approved for marketing. Consequently, the average cost per successful drug development program remains unacceptably high. This average cost per successful drug development is high in part because most of the invested capital spent per drug is related to drug failures along the pipeline development path.

[0102] An important reason for the high failure rate in clinical trials is the poor predictive value of currently used screening technologies for biological validation, pharmacological testing, and screening for success or failure of chemical entities and biologies in clinical trials involving human subjects. These screening technologies are based on in vitro cell-based screening models and in vivo animal models, which often lack or inadequately represent the clinical disease phenotype of the patients in which the tested chemical entities or biologies are intended to be used in the future. Therefore, success of these chemical entities or biologies in these models does not necessarily translate into clinical success in patients. Hence, the majority of chemical entities or biologies, while successful in these preceding screening and animal models, fail in clinical trials, particularly in late phase II and phase III trials (see, e.g., New Drug Development: A Regulatory Overview, Revised 5th edition. Ed. Mathieu M . Parexel, publishers). It has been estimated that more than 90% of new chemical entities (NCEs) fail in clinical trials, of which approximately two thirds fail for pharmacodynamic reasons (lack of efficacy and/or an unacceptable adverse event profile), the remaining third fail for pharmacokinetic reasons (see, e.g., Houlihan, Lokey, Howard& Zukin, Advanced Valuation Techniques in Life Sciences, February 2001).

DB1/ 694375 16.1 [0103] Accordingly, many needs remain unmet in various aspects of drug development and disease treatment, including drug discovery, validation of candidate therapeutic targets, diagnosis and/or clinical classification of patients.

BRIEF SUMMARY OF THE INVENTION

[0104] The invention provides, at least in part, biomarkers and methods of use thereof which aid the clinician in identifying those patients most likely to benefit from certain treatment regimens. The markers disclosed herein are also useful in assays to identify therapeutic agents useful for the treatment of malignancy, including breast cancer and prostate cancer.

[0105] In one aspect, the application discloses gene sets comprising genes which are differentially expressed in test samples derived from subjects having cancer, including subjects having different classes of cancer or subtypes of the same cancer, including subjects having different subtypes of breast cancer. In certain embodiments, the cancer subtypes are associated with different clinical outcomes or prognoses. Depending on the expression level of the genes in a test sample (derived from the cancer patients or from NCI-60 cell lines), the cancer (e.g., breast cancer) subtype is predicted to be associated with a good prognosis, a mixed prognosis or a poor prognosis. In alternative embodiments, the cancer subtypes are differentially associated with recurrence and/or metastasis and/or overall survival.

[0106] Accordingly, in one aspect, the application provides a method of diagnosing a cancer, including breast cancer, and/or a cancer subtype in a cancer patient.

[0107] In another embodiment the application provides a method of providing a prognosis. In one embodiment, the method comprises (a) culturing cancer cells derived from a sample obtained from a cancer patient in the presence of a set of at least one high-energy metabolite; and (b) assessing gene expression levels in the cultured cancer cells; and (c) comparing the gene expression levels of the cancer cell culture with the gene expression levels in a control sample, whereby a difference between the gene expression levels in the cancer cell culture and the gene expression levels of the control cell culture is indicative of the clinical outcome. In one embodiment, the application provides a method of predicting or diagnosing recurrence. In another embodiment the application provides a method of predicting metastasis. In yet another embodiment the application provides a method of predicting decreased overall survival.

[0108] In some embodiments, the application provides genes whose expression levels correlate to benign or malignant states in various cells and/or tissues, including the epithelial cells, including mammary epithelial cells (e.g., carcinoma), the bone, the muscle and other connective D 1/ 09437516.1 tissues (e.g., sarcoma), the lymphatic system (e.g., lymphoma), the blood cells and/or blood precursor cells (e.g., leukemia) and the pigment-providing cells (e.g., melanoma). In some embodiments the tumor cell is breast cancer tumor cell.

[0109] Another aspect of the present invention provides a method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which inhibits metabolite-induced gene expression pattern of at least a set of genes selected from those listed in at least one table from selected from Tables 1-7, wherein the set of genes are expressed cancer cells, derived from the cancer patient, cultured in the presence of at least one or more metabolites, wherein the therapeutic agent which inhibits metabolite-induced gene expression pattern is selected for treating the cancer patient.

[0110] A method for evaluating gene expression, the method comprising treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as ketones or lactate); and assessing changes in gene expression resulting from the treatment with said set of at least one high-energy metabolite; wherein said method comprises generating labeled polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one high-energy metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

[0111] In an aspect, the present invention provides a method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one high-energy metabolite, the method comprising: (a) subjecting a cancer in vitro cell culture to treatment with the set of at least one high-energy metabolite; (b) thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture; whereby a difference between the level of gene expression in the cancer cell culture and the level of gene expression in the control cell culture is an indication that gene expression of the set of at least one cancer associated gene is induced by the set of at least one high-energy metabolite; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

BRIEF DESCRIPTION OF THE DRAWINGS

DBl/ 69437516.1 [0112] Figure 1: HeatMaps for the Intersection Between MCF7 Lactate-Induced Genes and Transcripts that are Highly Expressed in Neural Stem Cells;

[0113] Figure 2: HeatMaps for the Intersection Between MCF7 Ketone-Induced Genes and Transcripts that are Highly Expressed in Hematopoietic Stem Cells;

[0114] Figure 3: Venn Diagrams for the Transcriptional Overlap between the Lactate-Induced and Ketone-Induced Transcriptional Profiles in MCF7 Cells;

[0115] Figure 4: HeatMaps for the Intersection Between MCF7 Lactate-Specific Genes and Transcripts that are Highly Expressed in Poor Prognosis Cancers;

[0116] Figure 5: The Lactate-Induced Gene Signature Is Associated with ER(+) Breast Cancer and Predicts Poor Clinical Outcome;

[0117] Figure 6: The Ketone-Induced Gene Signature Is Associated with ER(+) Breast Cancer and Predicts Poor Clinical Outcome;

[0118] Figure 7: The Lactate-Induced Gene Signature Predicts Recurrence, Metastasis, and Decreased Overall Survival in Luminal A Breast Cancers;

[0119] Figure 8: The Ketone-Induced Gene Signature Predicts Recurrence, Metastasis, and Decreased Overall Survival in Luminal A Breast Cancers;

[0120] Figure 9: The Ketone- and Lactate-Induced "Stem Cell" Signatures Predict Decreased Overall Survival in Luminal A Breast Cancers;

]0121] Figure 10: Survival Analysis for the Intersection Between MCF7 Lactate-Specific Genes and Transcripts that are Highly Expressed in Poor Prognosis Cancers;

[0122] Figure 11: Lactate and Ketones Increase Histone Acetylation in MCF7 Cancer Cells. MCF7 cells were treated with ketones and lactate;

[0123] Figure 12: Ketones and Lactate Promote the Growth of Mouse Embryonic Stem (ES) Cells in Culture;

[0124] Figure 13: A New Metabolic Strategy for Personalized Cancer Diagnosis and Therapy; and

[0125] Figure 14: Possible Mechanism(s) of Action of Ketones and Lactate: Converging on Acetyl-CoA. DB 1/ 69437516.1 DETAILED DESCRIPTION OF THE INVENTION

[0126] The present subject matter will now be described more fully hereinafter with reference to the accompanying Figures and Examples, in which representative embodiments are shown. The present subject matter can, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided to describe and enable one of skill in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the subject matter pertains. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0127] Surprisingly, it has been discovered that a clinical outcome in cancer, in particular breast cancer, could be determined by epigenetics and energy metabolism, rather than by the accumulation of specific "classical" gene mutations. Thus, it is now possible, with the materials, procedures and methods described herein, to expedite discovery of: new cancer biomarkers, new therapeutic targets, leading to elucidation of oncogenic mechanisms; and to facilitate classification of patients based on gene expression profile, disease prognosis and/or patients' therapeutic response.

[0128] It has been discovered that certain metabolites affect tumor cell behavior, including tumor-regenerating capacity and tumor progression. As any type of cell in the body can become a source of cancer, the tumor cell could be of any suitable cell type. Suitable tumor cell types include, but are not limited to those derived from, cancer of the epithelial cells (carcinoma), cancer of the bone, muscle or other connective tissues (sarcoma), cancer of the lymphatic system (lymphoma), cancer of blood cells or blood precursor cells (leukemia) and cancer of the pigment- providing cells (melanoma). In some embodiments the tumor cell is breast cancer tumor cell.

[0129] Tumor cells suitable for use with the methods disclosed can be derived from any cancer cells, including the NCI-60 cell lines having diverse tissue of origin: e.g., lung: NCI-H23, NCI- H522, A549-ATCC, EKVX, NCI-H226, NCI-H332M, H460, H0P62, and HOP92; colon: HT29, HCC-2998, HCT1 16, SW620, COLO205, HCT15, and KM12; breast: MCF7, MCF7ADRr, MDAMB23 , HS578T, MDAMB435, MDN, BT549, and T47D; ovarian: OVCAR3, OVCAR4, OVCAR5, OVCAR8, IGROV1, and SKOV3; leukemia: CCRFCEM, K562, MOLT4, HL60, RPMI8266, and SR; renal: U031, SN12C, A498, CAKI1, RXF393, 7860, ACHN, and TK10; melanoma: LOXIMVI, MALME3M, SKMEL2, SKMEL5, SKMEL28, M14, UACC62, and UACC257; prostate: PC3, DU145; CNS: SNB19, SNB75, U251, SF268, SF295, and SM539.

DB1/ 69437516.1 [0130] Additional suitable rumor cells include: Non-Small Cell Lung (LXFL 529); Small Cell Lung (DMS 114, and SHP-77); Colon (DLD-1 and KM20L2); CNS (SNB-78, and XF 498); Melanoma (RPMI-7951, and M19-MEL); Renal (RXF-631 and SN12K1); and Leukemia (P388, and P388/ADR).

[0131] Traditionally, cancer classification has been based on histopathological and clinical data. New technologies, however, have enabled genome-wide analysis of gene expression patterns, which have suggested that individual cancer phenotypes, including leukemia and breast cancer, exhibit characteristic expression profiles (see, e.g. Golub T. R. et al. "Molecular classification of cancer: class discovery and class prediction by gene expression monitoring," Science 1999 (Wash. DC), 286, 53 1-537; and Gruvberger S. et al. "Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns," Cancer Res., 61, 5979-5984).

[0132] Accordingly, in one aspect the present invention provides a new approach to personalized cancer medicine which incorporates features of both (i) cell metabolism and (ii) gene transcriptional profiling. In one embodiment a method is provided for identifying a mammalian cell as neoplastic or predisposed to neoplasia. The method comprising detecting metabolite-induced gene signature of a set of at least one or more genes listed in one or more of Tables 1-7 in a test cell derived from a sample obtained from a subject having cancer or suspected of having cancer. The test cell is identified as neoplastic or predisposed to neoplasia based on the detected level of the metabolite-induced gene signature(s).

[0133] Suitable metabolites include those derived from carbohydrates, fats and lipids and proteins. Suitable carbohydrates include monosaccharides, including include glucose (dextrose), fructose (levulose), galactose, xylose and ribose; disaccharides, including sucrose; and polysaccharides, including starch.

[0134] Other suitable metabolites include various intermediary glycolysis products as well as end-products of glycololysis. These include: glucose-6-phosphate; fructose-6-phosphate; fructose- 1,6-bisphosphate; fructose- 1,6-biphosphate; glycerone-phosphate (or dihydroxyacetone- phosphate); glyceraldehyde-3-P ("GAP"); glyceron-phosphate ("DHAP"); glycerate-1,3- biphosphate; glycrate-l,3-biphosphate converted to 3-phosphoglycerate; glycerate-2-phosphate; phosphoenolpyruvate; pyruvate; pyruvic acid; lactate; and lactic acid.

[0135] Other suitable metabolites includes glutamine and precursor compounds.

DBl/ 69437516.1 [0136] In an embodiment, the method for identifying a mammalian cell as neoplastic comprises detecting in a test mammalian cell (e.g. breast cancer cell) a level of gene expression pattern or activity, wherein the level of gene expression pattern or activity is induced by a set of at least one high-energy metabolite (e.g., 3-hydroxybutyrate or lactate); and identifying the test mammalian cell as neoplastic when a difference between the level of gene expression pattern or activity in the test mammalian cell and a corresponding level of gene expression pattern or activity in a control mammalian cell is detected.

[0137] At least two cancer models have been put forward to explain tumor heterogeneity and inherent differences of tumor-regenerating capacity (see, e.g., Visvader J. E. and Lindeman G. J. "Cancer stem cells in solid tumours: accumulating evidence and unresolved questions," Nat. Rev. Cancer. 2008, 8(10), 755-768). The clonal selection model of carcinogenesis implies that a random solitary cell undergoes malignant transformation, accumulates multiple mutations and subsequently acquires a survival advantage, which leads to clonal selection (see, e.g., Nowell P. C. "The clonal evolution of tumor cell populations," Science 1976, 194(4260), 23-28; and Campbell L. L. and Polyak K. "Breast tumor heterogeneity: cancer stem cells or clonal evolution?" Cell Cycle 2007, 6(19), 2332-2338). In contrast, the cancer stem cell ("CSC") hypothesis regards malignant transformation as a process, occurring in a subset of normal stem cells with pluripotent properties, which underlie deregulation of self-renewal pathways (see, e.g., Bonnet D. and Dick J. E. "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell," Nat. Med. 1997, 3(7), 730-737; and Reya T. and Clevers H. "Wnt signalling in stem cells and cancer," Nature 2005, 434(7035), 843-850).

[0138] High energy metabolites, including glutamine, lactate and ketones, including 3- hydroxybutyrate, acetoacetate, possibly promote tumor cell growth and tumor metastasis in vivio (including experimental metastasis of human breast cancer cells (e.g., Michigan Cancer Foundation-7 or MCF7) in in vivo xenograft models) by driving oxidative mitochondrial metabolism in cancer cells.

[0139] In order to understand how high energy metabolites affect tumor cell behavior, mechanistic experiments were conducted. In one experiment, MCF7 cells were cultured with lactate or ketones and then subjected to transcriptional analysis (exon-array). Transcriptional gene expressional analysis revealed differences in global gene expression profiles of tumor and normal cells. The results showed increased transcriptional expression of gene profiles normally associated with "sternness" (e.g., the ability of self-renew and differentiate), including genes upregulated in embryonic stem (ES) cells, demonstrating that the end-products of glycolysis (e.g., ketones and lactate) modulate tumor growth and metastasis. DB1/¾437 5 16.1 [0140] Accordingly, in one aspect of the present invention, the detection of inappropriate activation of sternness genetic pathways can be used to diagnose cancer and to predict the likelihood of therapy success or failure. Inappropriate activation of "sternness" genes in cancer cells is associated with aggressive clinical behavior and increased likelihood of poor clinical outcome in cancer patients, including therapy failure, recurrence of cancer, cancer metastasis and decreased survival, including overall survival. Thus, elucidation of such inappropriate activation of "sternness" gene expression can guide design of personalized medicine, wherein cancer therapy is specifically tailored to a patient's individual needs.

[0141] In another aspect of the present invention provides a method for growing stem cells. The method comprises culturing stem cells in a culture medium in presence of a set of at least one metabolite. In one embodiment, the metabolite is selected from the group consisting of glutamine, 3-hydroxybutyrate, acetoacetate and lactate.

[0142] Any type of stem cell can be used with the methods of the present invention. Suitable stem cells include mesenchymal stem cells, human embryonic stem cells, and the like. Human pluripotential cells can be created using in vitro fertilization technologies (human embryonic stem cells or HESC) (see, e.g. Thomson J. A et al. "Embryonic stem cell lines derived from human blastocysts," Science 1998, 282, 1145-1147), from parthenogenesis the chemical activation of human oocytes (parthenogentically derived embryonic stem cells or PGESC) (see, e.g., Cibelli J. B. et al. "Parthenogenetic stem cells in nonhuman primates," Science 2002, 295, 819; and Vrana K. E. et al. "Nonhuman primate parthenogenetic stem cells," Proc. Natl. Acad. Sci. U S A 2003, 100 Suppl 1, 1191 1-1 1916), from isolated human germ cells (primordial germ cells or PGC) (see, e.g., Shamblott M. J. et al. "Derivation of pluripotent stem cells from cultured human primordial germ cells," Proc Natl. Acad. Sci. USA 1998, 95,13726-13731), or from human amniotic fluid (human amniotic fluid derived stem cells or HAFSC).

[0143] In an embodiment, the neoplasm is breast cancer. Tissues in the body that are responsive to estrogens are called "estrogen-sensitive" or "estrogen-responsive" tissues and include cells of the urogenital tract, cardiovascular system and skeletal system. The cells that comprise estrogen-sensitive tissues contain estrogen receptors (ER). ER play significant roles in certain human disease states, breast cancer being one specific example. Cells in female breast tissue normally contain ER. Interaction of estrogens with ER in breast cells normally causes the breasts to grow at puberty and again during pregnancy. Since breast cells normally contain ER, it is not surprising that cells comprising tumors of the breast also contain ER. It has been estimated that 95% of all breast tumors, at least initially, have ER and are dependent on estrogens for growth. In such breast tumor cells, estrogens acting via the ER, dramatically escalate DBl/ 69437516.1 J proliferative and metastatic activity (Osborne, et al., 1980, Cancer, 46:2884-8). Moreover, ER (the estrogen or oestrogen receptor) negative breast tumours are general correlated with poorer

prognosis than ER positive tumours (see, e.g., Baselga and Norton, Cancer Cell 2002, 1, 319- 322).

[0144] In another embodiment, a metabolite such as lactate or 3-hydroxybutyrate is administered to cultured cancer cells, and changes in gene expression resulting from said treatment with the metabolite (lactate or 3-hydroxybutyrate) are assessed. In another embodiment, a ketone such as 3-hydroxybutyrate is administered to the cultured cancer cells, and changes in gene expression resulting from said treatment with the ketone are assessed. In another embodiment, the cancer cell cultures are exposed to a set of at least one or more metabolites of for about 12 hours to 48 hours. In yet another embodiment the level of gene expression is compared by transcriptional profiling following microarray analysis using a radio labeled probe. In yet another embodiment the levels of expression of a set at least 2000 to 5000 genes are compared. In another embodiment the level of expression of all the genes listed in Tables 1-7 are compared. In another embodiment the level of expression of a subset of all the genes listed in Tables 1-7 are compared.

[0145] In another aspect of the invention, a method is provided for reducing or inhibiting neoplastic growth of a mammalian cell which exhibits metabolite-induced transcription of a set at least one or more genes associated with a neoplasm. Expression of a polypeptide encoded by the metabolite-activated gene expression is reduced or inhibited in the mammalian cell by contacting the mammalian cell with a therapeutic agent that reduces or inhibits mitochondrial oxidative phosphorylation (e.g., an anti-oxidant). The set of genes is selected from those listed in Tables 1- 7. The growth of the cancer cells is reduced or inhibited through inhibition of upregulation of a set of at least one or more of the genes listed in Tables 1-7.

[0146] Suitable therapeutic agents for use with the methods of the present invention include metformin and Monocarboxylate Transporter (MCT1) inhibitors, including AR-C1 17977 and AR-C155858 and pharmaceutically acceptable salts thereof. AR-C155858 has the following structural formula.

DB 1/ 6943 75 16.1 [0147] Examples of suitable MCT1 inhibitors are disclosed in WO 2010/089580 (published 12 August 2010).

[0148] Adriamycin ® (generic name: Doxorubicin; another brand name: Rubex ®) is another example of a therapeutic agent that can be used with the methods disclosed herein. Cancers that can be treated with Adriamycin ® include bladder, breast, head and neck, leukemia, liver, lung, lymphomas, mesothelioma, multiple myeloma, neuroblastoma, ovary, pancreas, prostate, sarcomas, stomach, testis (germ cell), thyroid and uterus.

[0149] Another aspect of the invention provides a method for selecting a therapeutic strategy for treating a cancer patient. A set of one or more genes selected from those listed in Tables 1-7, whose expression in cancer cells of the patient is inhibited by an agent that reduces or inhibit oxidative mitochondrial metabolism is identified. A therapeutic agent which inhibits expression of the set of at least one or more genes is selected for treating the cancer patient.

[0150] In another aspect, the invention pertains to a method for evaluating gene expression wherein said method comprises treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as ketones or lactate); and assessing changes in gene expression resulting from the treatment with said set of at least one high-energy metabolite; wherein said method comprises generating labeled polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one high-energy metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

[0151] In an embodiment, a set of at least one high-energy metabolite is selected from ketones and lactate. In another embodiment the in vitro culture of cancer cells is treated with the set of at

least one high-energy metabolite for about 2 to 12 hours. In another embodiment the in vitro

DB 1/ 694375 16.1 culture of cancer cells is treated with the set of at least one high-energy metabolite for about 2 hours.

[0152] In another aspect, the present invention provides a method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one high- energy metabolite, the method comprising: (a) subjecting a cancer in vitro cell culture to treatment with the set of at least one high-energy metabolite; (b) thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture, whereby a difference between the level of gene expression in the cancer cell culture and the level of gene expression in the control cell culture is an indication that gene expression of the set of at least one cancer associated gene is induced by the set of at least one high-energy metabolite; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

[0153] In accordance with the present invention, there is provided a method for predicting a clinical outcome in a cancer patient, comprising (a) culturing cancer cells derived from a sample obtained from a cancer patient in the presence of a set of at least one high-energy metabolite; and (b) assessing gene expression levels in the cultured cancer cells; and (c) comparing the gene expression levels of the cancer cell culture with the gene expression levels in a control sample, whereby a difference between the gene expression levels in the cancer cell culture and the gene expression levels of the control cell culture is indicative of the clinical outcome.

[0154] In an embodiment, the clinical outcome is prognosis for survival. In alternative embodiments, the prognosis is a poor clinical outcome (e.g., shorter survival). In certain embodiments the poor clinical outcome is recurrence of cancer, increased/shorter survival of cancer, and/or cancer progression in the cancer patient. In alternative embodiments the clinical outcome is increased or decreased overall survival.

[0155] In accordance with another aspect, the present invention provides a method of stratifying a subject or a group of subjects having a cancer for a clinical trial, the method comprising: (a) treating an in vitro culture of cancer cells derived from a biological sample obtained from the subject or each member of the group of subjects having cancer with a set of at least one high-energy metabolite (such as ketones or lactate); (b) assessing changes in gene

DBl/ 69437516.1 expression induced by said set of at least one high-energy metabolite; (c) comparing the level of gene expression in the in vitro culture of cancer cells with a level of gene expression in a control cell culture; and (d) stratifying the subject or the group of subjects for a clinical trial on the basis of a difference between the level of gene expression in the in vitro culture of cancer cells and the level of gene expression in the control cell culture.

[0156] Those of ordinary skill in the art will be familiar with a variety of methods for assessing gene expression levels in tissue and/or biological fluid samples. In certain embodiments, assessing gene expression levels comprises (a) subjecting a spatially discrete microregion of an intact tissue sample to one or more physical or chemical treatments; and (b) assessing the gene expression levels in a nucleic acid sample from the microregion. If two or more spatially discrete microregions are assessed, then the gene expression levels of the different microregions may be compared. Assessing may also comprise immunologic detection of a gene or gene product (e.g., protein) or quantitative detection of an RNA (e.g., quantitative RT-PCR, Northern blotting) encoding a gene product (e.g., protein).

[0157] As will be appreciated by those of skill in the art, proteomics techniques can be used analyze and define the biomarkers of the present invention. In other words, instead of gene expression profiling can be conducted in terms of proteins, the products of the expressed genes. Accordingly, in certain embodiments, proteomics can be used to discover suitable biomarkers for use with the present invention. Proteomics is, among other things, the study of the proteome, the protein complement of the genome. The term proteome is also used to refer to the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as "expression proteomics")- Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. by mass spectrometry and/or N-terrninal sequencing, and (3) analysis of the data using bioinformatics. Proteomics methods are valuable supplements to other methods of gene expression profiling, and can be used, alone or in combination with other methods of the present invention, to detect the biomarkers of the present invention.

I. Definitions

[0158] As used herein, the following terms have the meanings ascribed to them unless specified otherwise. The term "cancer" is intended to include any member of a class of diseases characterized by the uncontrolled growth of aberrant cells. The term includes all known cancers

DB / 694375 16 . and neoplastic conditions, whether characterized as malignant, benign, soft tissue, or solid, and cancers of all stages and grades including pre- and post-metastatic cancers. Examples of different types of cancer include, but are not limited to, lung cancer (e.g., non-small cell lung cancer); digestive and gastrointestinal cancers such as colorectal cancer, gastrointestinal stromal tumors, gastrointestinal carcinoid tumors, colon cancer, rectal cancer, anal cancer, bile duct cancer, small intestine cancer, and stomach (gastric) cancer; esophageal cancer; gallbladder cancer; liver cancer; pancreatic cancer; appendix cancer; breast cancer; ovarian cancer; renal cancer (e.g., renal cell carcinoma); cancer of the central nervous system; skin cancer; lymphomas; choriocarcinomas; head and neck cancers; osteogenic sarcomas; and blood cancers. As used herein, a "tumor" comprises one or more cancerous cells.

[0159] As used herein, the term "profile" includes any set of data that represents the distinctive features or characteristics associated with a tumor, tumor cell, and/or cancer. The term encompasses a "nucleic acid profile" that analyzes one or more genetic markers, a "protein profile" that analyzes one or more biochemical or serological markers, and combinations thereof. Examples of nucleic acid profiles include, but are not limited to, a genotypic profile, gene copy number profile, gene expression profile, DNA methylation profile, and combinations thereof. Non-limiting examples of protein profiles include a protein expression profile, protein activation profile, and combinations thereof. For example, a "genotypic profile" includes a set of genotypic data that represents the genotype of one or more genes associated with a tumor, tumor cell, and/or cancer. Similarly, a "gene copy number profile" includes a set of gene copy number data that represents the amplification of one or more genes associated with a tumor, tumor cell, and/or cancer. Likewise, a "gene expression profile" includes a set of gene expression data that represents the mRNA levels of one or more genes associated with a tumor, tumor cell, and/or cancer. In addition, a "DNA methylation profile" includes a set of methylation data that represents the DNA methylation levels (e.g., methylation status) of one or more genes associated with a tumor, tumor cell, and/or cancer. Furthermore, a "protein expression profile" includes a set of protein expression data that represents the levels of one or more proteins associated with a tumor, tumor cell, and/or cancer. Moreover, a "protein activation profile" includes a set of data that represents the activation (e.g., phosphorylation status) of one or more proteins associated with a tumor, tumor cell, and/or cancer.

[0160] With regard to nucleic acids used in the invention, the term "isolated nucleic acid" is sometimes employed. This term, when applied to DNA, refers to a DNA molecule that is separated from sequences with which it is immediately contiguous (in the 5 1 and 3' directions) in the naturally occurring genome of the organism from which it was derived. For example, the

DB / 694375 6.1 "isolated nucleic acid" may comprise a DNA molecule inserted into a vector, such as a plasmid or virus vector, or integrated into the genomic DNA of a prokaryote or eukaryote. An "isolated nucleic acid molecule" may also comprise a cDNA molecule. An isolated nucleic acid molecule inserted into a vector is also sometimes referred to herein as a recombinant nucleic acid molecule.

[0161] For purposes of the present invention, "a" or "an" entity refers to one or more of that entity; for example, "a cDNA" refers to one or more cDNA or at least one cDNA. As such, the terms "a" or "an," "one or more" and "at least one" can be used interchangeably herein. It is also noted that the terms "comprising," "including," and "having" can be used interchangeably. Furthermore, a compound "selected from the group consisting of refers to one or more of the compounds in the list that follows, including mixtures (i.e. combinations) of two or more of the compounds. According to the present invention, an isolated, or biologically pure molecule is a compound that has been removed from its natural milieu. As such, "isolated" and "biologically pure" do not necessarily reflect the extent to which the compound has been purified. An isolated compound of the present invention can be obtained from its natural source, can be produced using laboratory synthetic techniques or can be produced by any such chemical synthetic route.

[0162] The term "oligonucleotide," as used herein is defined as a nucleic acid molecule comprised of two or more ribo- or deoxyribonucleotides, preferably more than three. The exact size of the oligonucleotide will depend on various factors and on the particular application and use of the oligonucleotide. Oligonucleotides, which include probes and primers, can be any length from 3 nucleotides to the full length of the nucleic acid molecule, and explicitly include every possible number of contiguous nucleic acids from 3 through the full length of the polynucleotide. Preferably, oligonucleotides are at least about 10 nucleotides in length, more preferably at least 1 nucleotides in length, more preferably at least about 20 nucleotides in length.

[0163] The term "probe" as used herein refers to an oligonucleotide, polynucleotide or nucleic acid, either RNA or DNA, whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, which is capable of annealing with or specifically hybridizing to a nucleic acid with sequences complementary to the probe. A probe may be either single-stranded or double-stranded. The exact length of the probe will depend upon many factors, including temperature, source of probe and use of the method. For example, for diagnostic applications, depending on the complexity of the target sequence, the oligonucleotide probe typically contains 15-25 or more nucleotides, although it may contain fewer nucleotides. The probes herein are selected to be complementary to different strands of a particular target nucleic acid sequence. DB 1/ 69437516.1 This means that the probes must be sufficiently complementary so as to be able to "specifically hybridize" or anneal with their respective target strands under a set of pre-determined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target. For example, a non-complementary nucleotide fragment may be attached to the 5' or 3' end of the probe, with the remainder of the probe sequence being complementary to the target strand. Alternatively, non-complementary bases or longer sequences can be interspersed into the probe, provided that the probe sequence has sufficient complementarity with the sequence of the target nucleic acid to anneal therewith specifically.

[0164] The term "primer" as used herein refers to an oligonucleotide, either R A or DNA, either single-stranded or double-stranded, either derived from a biological system, generated by restriction enzyme digestion, or produced synthetically which, when placed in the proper environment, is able to functionally act as an initiator of template-dependent nucleic acid synthesis. When presented with an appropriate nucleic acid template, suitable nucleoside triphosphate precursors of nucleic acids, a polymerase enzyme, suitable cofactors and conditions such as a suitable temperature and H, the primer may be extended at its 3' terminus by the addition of nucleotides by the action of a polymerase or similar activity to yield a primer extension product. The primer may vary in length depending on the particular conditions and requirement of the application. For example, in diagnostic applications, the oligonucleotide primer is typically 15-25 or more nucleotides in length. The primer must be of sufficient complementarity to the desired template to prime the synthesis of the desired extension product, that is, to be able anneal with the desired template strand in a manner sufficient to provide the 3' hydroxyl moiety of the primer in appropriate juxtaposition for use in the initiation of synthesis by a polymerase or similar enzyme. It is not required that the primer sequence represent an exact complement of the desired template. For example, a non-complementary nucleotide sequence may be attached to the 5 end of an otherwise complementary primer. Alternatively, non- complementary bases may be interspersed within the oligonucleotide primer sequence, provided that the primer sequence has sufficient complementarity with the sequence of the desired template strand to functionally provide a template -primer complex for the synthesis of the extension product.

II. Detection Of Biomarkers

[0165] The biomarkers of this invention can be detected by any suitable method. Detection paradigms that can be employed to this end include optical methods, electrochemical methods (voltametry and amperometry techniques), atomic force microscopy, and radio frequency methods, e.g., multipolar resonance spectroscopy. Illustrative of optical methods, in addition to DB 1/ 694375 16.1 microscopy, both confocal and non-confocal, are detection of fluorescence, luminescence, chemiluminescence, absorbance, reflectance, transmittance, and birefringence or refractive index (e.g., surface plasmon resonance, ellipsometry, a resonant mirror method, a grating coupler waveguide method or interferometry).

[0166] In certain embodiments of the present invention genetic events such as altered gene expression level and alternative splicing are detected. Common detection methods include gene- and exon-level expression and exon-level expression. In particular, Affymetrix GeneChip® Exon Arrays can be used to examine alternative splicing. Affymetrix GeneChip® 3' Expression Arrays, Exon Array, Promoter Tiling Arrays and Whole-Genome Tiling Arrays all can be used to examine altered gene expression level.

[0167] III. Gene Expression Profiling

[0168] A gene expression profile is typically evaluated in vitro on a sample collected from a subject in comparison to a normal or reference sample. Determination of a transcriptional expression profile can be accomplished, e.g., using hybridization techniques well-known to those skilled in the art such as Northern analysis and slot blot hybridization or by performing reverse- transcriptase (RT)-PCR amplification followed by gel electrophoresis. Applicable PCR amplification techniques are described in Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., New York (1999); Theophilus et al., "PCR Mutation Detection Protocols," Humana Press (2002); and Innis et al., "PCR Applications: Protocols for Functional Genomics," 1st Edition, Academic Press (1999). General nucleic acid hybridization methods are described in Anderson, "Nucleic Acid Hybridization," BIOS Scientific Publishers (1999). Amplification or hybridization of a plurality of transcribed nucleic acid sequences (e.g., mRNA or cDNA) can also be performed using mRNA or cDNA sequences arranged in a microarray. Microarray methods are generally described in Hardiman, "Microarrays Methods and Applications: Nuts & Bolts," DNA Press (2003) and Baldi et al., "DNA Microarrays and Gene Expression: From Experiments to Data Analysis and Modeling," Cambridge University Press (2002).

[0169] The measurement of gene expression profiles using microarrays also has many important applications to the monitoring of disease states and therapies, the identification of drug targets, the identification of pathways of drug action, and drug design. In particular, measurement of gene expression profiles using microarrays can be used to identify "good prognosis" and "poor prognosis" gene expression signatures, which can be used to predict the clinical outcome of cancer patients, including breast cancer patients. The microarray gene

DBl/ 69437516.1 expression profiles can also be used to evaluate the target specificity of a candidate drug by comparison of an expression profile obtained from cells treated with the candidate drug to a database of expression profiles obtained from cells treated with known drugs (see, e.g., U.S. Patent No. 5,777,888).

[0170] Comparing patterns of gene expression is a widely used means of identifying novel genes, investigating gene function, and finding potential new therapeutic targets (see, e.g., Shiue et al., Drug Devel. Res. 1997, 4 1,142-159). Many techniques have been used to identify and clone differentially expressed genes (see, e.g., Liang et al. Science 1992, 257, 967-971; Welsh et al. Nucleic Acids Res. 1992, 20, 4965-4970; Tedder et al. Proc. Natl. Acad. Sci. 1988, 85, 208- 212; Davis et al. Proc. Natl. Acad. Sci. 984, 81, 2 194-2 198; Lisitsyn et al. Science 993, 259:946-951; Velculescu et al. Science 1995, 270:484-487; Diatchenko et al. Proc. Natl. Acad. Sci. 1996, 93, 6025-6030; Jiang et al., Proc. Natl. Acad. Sci. 2000, 97,12684-12689; Yang et al. Nucleic Acids Res. 1 99, 27, 517-523).

[0171] Other techniques, including cDNA microarray hybridization have been used to quantify the expression of many thousands of discrete mRNA or cDNA sequences in a single assay known as expression profiling (see, e.g., van't Veer et al. Nature 2002, 415, 530-536; Hughes et al. Nature Biotech. 2001, 19, 342-347; Hughes et al. Cell 2000, 102,109-126; Lockhart and Winzeler, Nature 2000, 405, 827-836; Roberts et al. Science 2000, 287, 873-880; Wang et al. Gene 1999, 229, 101-108; Lockhart et al. Nat. Biotech. 1996, 14, 1675-1680; Schena et al. Science 1995, 270, 467-470; and U.S. Patent No. 6,040,138). For example, EGFR mRNA levels can be measured in tumor samples by microarray hybridization as described in Bhargava et al., Mod. Pathol. 2005, 18,1027-1033. In certain embodiments, a gene expression microarray groups genes according to similarities in patterns of gene expression in expression profiling experiments.

[0172] In addition, gene expression profiles can be used to identify pathway-specific reporters and target genes for a particular biological pathway of interest. Such reporter genes and probes directed to them can be used to measure the activity of a particular biological pathway and may be further used in the design of drugs, drug therapies, or other biological agents to target a particular biological pathway. Gene expression profiles can also be used to determine protein activity levels of a target protein using the methods described in U.S. Patent No. 6,324,479.

IV. EXAMPLES

[0173] Example 1: Culture of MCF7 Cells and Treatment with Lactate and Ketones:

DB1/ 69437 5 16. 1 The estrogen receptor positive ceil line MCF7 was purchased from ATCC. Cells were maintained in DMEM, with 10% Fetal Bovine Serum (FBS) and Penicillin 100 units/mL-Streptomycin 100 µg/mL (Invitrogen) [DMEM 10% FBS-Pen-Strep]. Cells were cultured in a humidified atmosphere containing 5% C02 at 37°C. Briefly, 1.4 x 10 MCF7 cells were plated in 10 cm plastic dishes (Corning) in DMEM 10% FBS-Pen-Strep. After 24 hours, the media of these cells was changed to DMEM with 10% NuSerum (a low protein alternative to FBS; BD Biosciences)

and Pen-Strep with or without 10 mM L-lactate (sodium salt; Sigma cat. #71718), or 10 mM R-3- hydroxy-butyrate (sodium salt; Sigma cat. #298360). Cells were maintained in this media for 48 hours before gene expression profiling was performed. Acetylation-specific antibodies directed against histone proteins were obtained from Cell Signaling Technology, Inc. [0174] Example 2: Genome-wide Transcriptional Profiling (Exon-arrav):

Total RNA was extracted using the RNeasy protocol from Qiagen (Valencia, California, USA). RNA was prepared from three control MCF7 samples, and three MCF7 samples treated with lactate, and three MCF7 samples treated with ketones. RNA quality was evaluated using the Agilent 2 00 Bioanalyzer (Agilent, Palo Alto, California, USA). RNA amplification and labeling was performed from 50 ng total RNA by the WT-Ovation Pico RNA amplification system (NuGen Technologies, Inc.). Amplified cDNA was purified with QIAGEN QIAquick PCR purification Kit. Sense transcript cDNA (ST-cDNA) was generated from 3 amplified cDNA using WT-Ovation Exon module (NuGen Technologies, Inc.). Purified ST-cDNA was assed for yield using the Nanodrop Spectrophotometer (NanoDrop Technologies, Inc.). 5 ST-cDNAs were fragmented and chemically labeled with biotin to generate biotinylated ST-cDNA using FL- Ovation cDNA biotin module V2 (NuGen Technologies, Inc.). Each Affymetrix Human Exon (HuEx-1.0-st-v2) array (Affymetrix, Santa Clara, CA) were hybridized with fragmented and biotin-labeled target (4.5 µg) in 200 µΐ of hybridization cocktail. Target denaturation was performed at 99°C for 2 min. and then 45°c for 5 min., followed by hybridization for 18 hrs. Arrays then were washed and stained using Genechip Fluidic Station 450, and hybridization signals were amplified using antibody amplification with goat IgG (Sigma-Aldrich) and anti- streptavidin biotinylated antibody (Vector Laboratories, Burlingame, CA, USA). Chips were scanned on an Affymetrix Gene Chip Scanner 3000, using Command Console Software. Background correction and normalization were done using Robust Multichip Average (RMA) with Genespring V 11.5 software (Agilent, Palo Alto, CA, USA). Results from one exon for each gene analyzed were selected for inclusion in Supplemental Tables 1 and 2. A p-value of <0.05 was considered statistically significant.

[0175] Example 3: Analysis of Clinical Outcome in Human Breast Cancer Patients:

DB 1/ 694375 16.1 A microarray dataset that was previously compiled from the public repositories Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) 48 and ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) 4 was used to evaluate the Ketone and Lactate expression signatures in the context of clinical samples ' . Only samples with E IHC data were selected for analysis, including 967 ER-positive and 325 ER-negative, for a total of 1292 samples. Samples were first analyzed in subsets based on their ER IHC status. Additional subsets were defined by classifying samples among five canonical breast cancer subtypes, including luminal A, luminal B, normal-like, basal, and Her-2-overexpressing disease. Samples were classified by computing their correlation against five expression profile centroids representing these breast cancer subtypes and assigning and assigning them to the subtype with the highest corresponding correlation coefficient 2. Samples with a maximum correlation coefficient below 0.3 were considered unclassified. Differential expression of the averaged gene signature magnitude among these sample subsets was evaluated using two-tailed t-test. Kaplan-meier analysis was used to evaluate survival trends within sample subsets, including 627 samples with metastasis- free survival time (507 ER-pos., 120 ER-neg.), 637 with relapse free survival time (517 ER-pos., 120 ER-neg.), and 329 with overall survival time (219 ER-pos., 110 ER-neg.). The Log-rank test was used to evaluate differences in survival curves for high vs. low signature-expressing populations.

[0176] Example 4 : Murine Embryonic Stem ES Ce Culture:

Rl cells (a kind gift of Dr. S. McMahon, Thomas Jefferson University, Philadelphia, PA), are mouse embryonic stem cells and were cultured on tissue culture plates (BD Falcon, Franklin Lakes, NJ) coated with 0.1% (v/v) porcine gelatin (Sigma-Aldrich Corp, St. Louis, MO) in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Grand Island NY) in the presence of 1 % fetal bovine serum (ES-tested Hyclone, Perbio, Logan, UT) 0.1 mM 2-mercaptoethanol, 0.1 mM non-essential aminoacids, 2 mM Glutamine, 0. ImM sodium pyruvate, 10 mM HEPES, and 1000 unit/ml murine LIF (Chemicon International Inc., Tamecula, CA) 100 units/ml penicillin and 100 µ/ml streptomycin. Cells were trypsinized and re-plated every 2nd day and re-fed daily. In some experiments 5 mM or 10 mM of (R)-(-)-l, 3-Butanediol; (R)-(-)-3-Hydroxybutyric acid; Sodium L-lactate (Sigma-Aldrich Inc., St. Louis, MO) was added to the medium. In all the experiments, medium was replaced daily. Alkaline phosphatase (AP) staining was performed using Fast Red TR salt™ (Sigma) reagent, according to the manufacturer's protocol. Computer- assisted image analysis of alkaline phosphatase positive colonies was performed using an Olympus BX51 System Microscope (Olympus Corp., Miami, FL, USA) equipped with a Micropublisher 5.0 cooled CCD camera (Qlmaging Corp., BC). ImageJ software was used to

DB 1/ 69437516.1 analyze colonies size. MEFs were inactivated to be used as a feeder layer for mouse ES cells. Mitotic inactivation was performed by mitomycin C treatment. Briefly, fibroblasts were grown to 90% confluence and mitomycin was added to the growth medium at final concentration of 10pg/ml. Cells were treated for 3h. MEFs were trypsinized, counted, and frozen at the concentration of 3 x 10 /ml. 1ml of frozen feeders was used to coat a 24 well plate. Al the ES cell experiments were performed at least 3 times in duplicate. Results were analyzed for statistical significance by the two tail Student's t-test.

[0177] Figures and Tables:

[0178] Reference is now made to Figure 1, which depicts HeatMaps for the intersection between MCF7 lactate-induced genes and transcripts that are highly expressed in neural stem cells. Note that these two gene sets have 461 intersecting genes in common. See Supplemental Table 4 for a detailed list. Overlapping genes are shown in panels A and B.

[0179] Reference is now made to Figure 2, which depicts HeatMaps for the intersection between MCF7 ketone-induced genes and transcripts that are highly expressed in hematopoietic stem cells. Note that these two gene sets have 311 intersecting genes in common. See Supplemental Table 5 for a detailed list.

[0180] Reference is now made to Figure 3, which illustrates Venn diagrams for the transcriptional overlap between the lactate-induced and ketone-induced transcriptional profiles in MCF7 cells. Transcriptional overlap between the lactate- and ketone-induced gene profiles is shown. Using this approach, -1,433 overlapping genes were identified; 2,698 genes were found to be lactate-specific, while 2,708 genes were found to be ketone-specific. Gene set enrichment analysis (GSEA) revealed that all three gene sets (common, lactate-specific, and ketone-specific) remained associated with sternness, although differences were noted. The lactate-specific gene profile was most similar to neural stem cells, while the ketone-specific gene profile was most similar to hematopoietic stem cells. The genes commonly upregulated by both lactate and ketones were most similar to embryonic stem cells. Finally, the lactate-specific gene profile also showed significant overlap with two clinical gene signatures that predict poor outcome in liver cancer and multiple myeloma. Associations with ER(+) and ER(-) breast cancers were also noted. See Supplemental Table 3.

[0181] Reference is now made to Figure 4, which depicts HeatMaps for the intersection between MCF7 lactate-specific genes and transcripts that are highly expressed in poor prognosis cancers. The lactate-specific gene profile showed significant overlap with two clinical gene

DBl/ 69437516.1 signatures that predict poor outcome in and multiple myeloma (MM, 37 genes overlap) and liver cancer (HCC, 31 genes overlap). See Supplemental Tables 6 and 7 for the detailed lists.

[0182] Reference is now made to Figure 5, which illustrates the lactate-induced gene signature is associated with ER(+) breast cancer and predicts poor clinical outcome. Figure 5A depicts Boxplots, which illustrate differential regulation of the lactate signature expression in breast cancer versus healthy breast tissue. Arrows indicate the directionality of differential regulation within each population. Figure 5B depicts Survival curves within low and high lactate signature-expressing populations, shown for overall survival in ER-positive breast cancer. This signature contains 4,131 genes (See Supplemental Table 1).

[0183] Reference is now made to Figure 6, which depicts the ketone-induced gene signature is associated with ER(+) breast cancer and predicts poor clinical outcome. Figure 6A shows Boxplots, which illustrate differential regulation of the ketone signature expression in breast cancer versus healthy breast tissue. Arrows indicate the directionality of differential regulation within each population. Figure 6B depicts Survival curves within low and high ketone signature-expressing populations, shown for overall survival in ER-positive breast cancer. This signature contains 4,141 genes (See Supplemental Table 2).

[0184] Reference is now made to Figure 7, which shows that the lactate-induced gene signature predicts recurrence, metastasis, and decreased overall survival in luminal a breast cancers. Survival curves within low and high lactate signature-expressing populations are shown within the luminal A subtype for metastasis-free survival (Figure 7A), relapse-free survival (Figure 7B), and overall survival (Figure 7C). This signature contains - 4,131 genes (See Supplemental Table 1). In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0185] Reference is now made to Figure 8, which shows that the ketone-induced gene signature predicts recurrence, metastasis, and decreased overall survival in luminal a breast cancers. Survival curves within low and high ketone signature-expressing populations are shown within the luminal A subtype for metastasis-free survival (Figure 8A), relapse-free survival (Figure 8B), and overall survival (Figure 8C). This signature contains - 4,141 genes (See Supplemental Table 2). In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0186] Reference is now made to Figure 9, which shows that the ketone- and lactate-induced "stem cell" signatures predict decreased overall survival in luminal a breast cancers. Survival

DBl/ 69437516.1 curves within low and high stem-cell specific ketone signature-expressing populations are shown for overall survival within ER-positive disease (Figure 9A), and the luminal A subtype (Figure 9B). Similar results are shown for the stem-cell specific lactate signature in panel C (Figure 9C), with reductions in overall survival. These two signatures each contain -300-400 gene transcripts, see Supplemental Tables 4 and 5. In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0187] Reference is now made to Figure 10, which shows that survival analysis for the intersection between MCF7 lactate-specific genes and transcripts that are highly expressed in poor prognosis cancers. Figure 10A illustrates Survival curves based on the intersection of the lactate and the HCC-derived signatures are shown within the luminal A subtype for overall survival. Figure 10B illustrates Survival curves based on the intersection of the lactate and the MM-derived signatures are shown for overall survival. These two signatures each contain -30- 40 gene transcripts, see Supplemental Tables 4 and 5. HCC, hepatocellular carcinoma; MM, multiple myeloma.

[0188] Reference is now made to Figure 11, which shows that lactate and ketones increase histone acetylation in MCF7 cancer cells. MCF7 cells were treated with ketones and lactate. Then, we used acetylation-specific antibody probes to assess that status of histone acetylation. Note that both ketones and lactate increased histone acetylation. However, lactate had a more positive effect than ketones, and both resulted in a "laddering" effect, which most likely represents hyper-acetylation plus other protein modifications, such as phosphorylation, which affects the mobility of proteins in SDS-PAGE gels. As such, the lactate- and ketone-induced increases in histone acetylation may contribute to changes in genome-wide transcriptional profiling. For histone H4, two panels are shown. One panel shows the higher molecular weight "laddering" species; the other panel shows a single band, which most likely represents the mono- acetylated species of histone H4, (3HB, 3-hydroxy-butryate; L-Lac, L-Lactate).

[0189] Reference is now made to Figure 12, which shows that ketones and lactate promote the growth of mouse embryonic stem (ES) cells in culture. In Figure 12A, Rl murine ES cells were grown in the absence or presence of various metabolites, then colony size and number were quantitated. In Figure 12B, representative images of ES cell colonies are shown. Note that both colony size and number were significantly increased (p < 0.01). Importantly, colony number increased up to 3-fold. BD, butanediol; 3HB, 3-hydroxy-butryate; L-Lac, L-Lactate.

[0190] Figure 13 illustratesa new metabolic strategy for personalized cancer diagnosis and therapy. Outlined is a general experimental strategy for personalized cancer medicine. Briefly,

DB 1/ 694375 16.1 cancer cells of a particular tumor type are selected for study. Then, these cancer cells are cultured in the absence and presence of high-energy metabolites, such as ketones and/or lactate. This should allow the investigator to generate a new gene signature based on transcriptional profiling (exon-array). This signature could then be used to select the patients that are undergoing this type of tumor metabolism, and correlate tumor metabolism with clinical outcome, such as recurrence and metastasis. High-risk patients could then be identified at diagnosis and treated with new therapies that are designed to target oxidative mitochondrial metabolism, such as metformin which is a specific inhibitor of mitochondrial complex I.

[0191] Though not wishing to be bound by theory, Figure 14 illustrates possible mechanism(s) of action of ketones and lactate, converging on Acetyl-CoA. Lactate and Ketones are converted to Acetyl-CoA, which can then be used via oxidative mitochondrial metabolism to generate high amounts of ATP. Alternatively, Acetyl-CoA could also be utilized for the acetylation of proteins, such as histones. Histone acetylation has been associated with increases in gene expression.

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Tables:

Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate Data Set P-value Detailed Description Stem Cells STEMCELL NEURAL UP 8.45E-23 Enriched in mouse neural stem cells, compared to differentiated brain and bone marrow cells STEMCELL EMBRYONIC UP 9.31E-17 Enriched in mouse embryonic stem cells, compared to differentiated brain and bone marrow cells STEMCELL HEMATOPOIETIC Enriched in mouse hematopoietic stem UP cells, compared to differentiated brain and bone marrow cells STEMCELL COMMON UP 9.95E-05 Enriched in mouse embryonic, neural and hematopoietic stem cells, compared to differentiated brain and bone marrow cells HSC LTHSC ADULT .94E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from adult bone marrow (LT-HSC Shared + Adult) HSC LTHSC FETAL 4.79E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from fetal liver (LT-HSC Shared) HSC LTHSC SHARED 4.79E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from both adult bone marrow and fetal liver (Cluster i, LT¬ HSC Shared)

DBl/ 69437516.1 Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate Data Set P-value Detailed Description HADDAD HSC CD 10 UP 1.46E-03 Genes upregulated in human hematopoietic stem cells of the line CD45RA(hi) Lin- CD10+, which are biased toward developing into B cells, versus CD45RA(int) CD7- and CD45RA(hi) CD7+. DNA Damage Response UVC XPCS ALL DN 4.57E-23 Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC UVC XPCS 8HR DN 7.07E-21 Down-regulated at 8 hours following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC UVC TTD ALL DN 9.84E-18 Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC UVC TTD 4HR DN 5.80E-15 Down-regulated at 4 hours following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC UVC XPCS 4HR DN 8.87E-1 1 Down-regulated at 4 hours following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC DNA Damage Response UVC TTD-XPCS COMMON DN Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD fibroblasts with 3 J/m 2 UVC UVB NHEK1 DN 2.47E-09 Downregulated by UV-B light in normal human epidermal keratinocytes UVC TTD 8HR DN 1.33E-08 Down-regulated at 8 hours following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC Breast Cancer BRCA ER NEG 8.50E-06 Genes whose expression is consistently negatively correlated with estrogen receptor status in breast cancer - higher expression is associated with ER-negative tumors Transcription Factors and Signaling Molecules Associated with Proliferation, Sternness, and Cell Migration GGGCGGR__V$SP1_Q6 8.22E-1 1 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl transcription factor GGGAGGRR_V$MAZ_Q6 2.68E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC-associated zinc finger protein (purine-binding transcription factor) TTGTTT V$FOX04 0 1 3. 17E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation DB1/ 69437 5 16.1 Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate Data Set P-value Detailed Description for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 7 CTTTGT_V$LEF1_Q2 7.86E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid enhancer-binding factor 1 Transcription Factors and Signaling Molecules Associated with Proliferation, Sternness, and Cell Migration CAGGTG_V$E12_Q6 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) SCGGAAGY V$EL 1 02 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif SCGGAAGY which matches annotation for ELK1: ELK1, member of ETS oncogene family GCM MAP4K4 139 Neighborhood of MAP4K4 mitogen- activated protein kinase kinase kinase kinase 4 in the GCM expression compendium HSA045 1O FOCAL ADHESION 1.55E-05 Genes involved in focal adhesion GCM ERBB2IP 53 2.54E-05 Neighborhood of ERBB2IP erbb2 interacting protein in the GCM expression compendium BRENTANI SIGNALING Cancer related genes involved in the cell signaling

Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones. Data Set P-value Detailed Description Stem Cells STEMCELL HEMATOPOIETIC 2.88E-09 Enriched in mouse hematopoietic stem UP cells, compared to differentiated brain and bone marrow cells STEMCELL EMBRYONIC UP 6.29E-04 Enriched in mouse embryonic stem cells, compared to differentiated brain and bone marrow cells STEMCELL NEURAL UP 6.74E-04 Enriched in mouse neural stem cells, compared to differentiated brain and bone marrow cells DNA Damage Response UVC XPCS ALL DN 2.75E-1 3 Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC UVC XPCS 8HR DN .39E-12 Down-regulated at 8 hours following treatment of XPB/CS fibroblasts with 3 DBl/ 69437516.1 Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones. Data Set P-value Detailed Description J/m 2 UVC UVC_XPCS_4HR_DN 5.34E-07 Down-regulated at 4 hours following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC UVC TTD ALL DN 6.87E-07 Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC UVC TTD 4HR DN 6.16E-06 Down-regulated at 4 hours following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC UVC_TTD_8HR_DN 2.07E-05 Down-regulated at 8 hours following treatment of XPB/TTD fibroblasts with 3 J/m 2 UVC UVB_NHEK 1_DN 2.45E-05 Downregulated by UV-B light in normal human epidermal keratinocytes UVB_NHEK3_C8 8.75E-05 Regulated by UV-B light in normal human epidermal keratinocytes, cluster 8 UVC LOW ALL DN 9.29E-05 Down-regulated at any timepoint following treatment of WS1 human skin fibroblasts with UVC at a low dose (10 J/m 2) (clusters cl-c5) Breast Cancer BRCA ER POS 1.15E-04 Genes whose expression is consistently positively correlated with estrogen receptor status in breast cancer - higher expression is associated with ER-positive tumors Transcription Factors and Signaling Associated with Proliferation, Sternness, and Migration GGGCGGR_V$SP1_Q6 1.00E-13 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl transcription factor CAGGTG_V$E12_Q6 7.79E-1 1 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) TTGTTT V$FOX04 0 1 2.37E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 7 HSA045 10 FOCAL ADHESION 3.76E-07 Genes involved in focal adhesion TGACAGNY VSMEISl 0 1 2.21E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TGACAGNY which matches annotation for MEIS1: Meisl, myeloid ecotropic viral integration site 1 homolog (mouse) DBl/ 69437516.1 Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones. Data Set P-value Detailed Description GGGAGGRR_V$MAZ_Q6 3.65E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC-associated zinc finger protein (purine-binding transcription factor) CTTTGT_V$LEF 1_Q2 4.63E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid enhancer-binding factor 1 Transcription Factors and Signaling Associated with Proliferation, Stemness, and Migration TCANNTGAY VSSREBP 1 01 1.09E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TCANNTGAY which matches annotation for SREBF1: sterol regulatory element binding transcription factor 1 GGGTGGRR V$PAX4 03 1.38E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGTGGRR which matches annotation for PAX4: paired box gene 4 TGACCTY_V$ERR1_Q2 1.59E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TGACCTY which matches annotation for ESRRA: estrogen-related receptor alpha HSA045 12__ECM_RECEPTOR N 1.08E-04 Genes involved in ECM-receptor TERACTION interaction

BRENTANI SIGNALING 1.06E-04 Cancer related genes involved in the cell signaling CELL ADHESION 3.70E-04 The attachment of a cell, either to another cell or to the extracellular matrix, via cell adhesion molecules. HSA04012_ERBB_SIGNALING_P Genes involved in ErbB signaling pathway ATHWAY

Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ankyrin repeat and sterile alpha motif domain ANKS1A containing 1A 13.893079 0.00129568 ubiquitin-conjugating enzyme E2D 2 UBE2D2 (UBC4/5 homolog, yeast) 11.637619 0.00544828 MGAT5 mannosyl (alpha- 1,6-)-glycoprotein beta- 1,6- 9.050858 0.00126631

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value N-acetyl-glucosaminyltransferase SRP19 signal recognition particle 19kDa 8.965928 0.00278124 EIF5B eukaryotic translation initiation factor 5B 8.853053 0.04053256 RAD50 RAD50 homolog (S. cerevisiae) 7.9411 5 0.00729083 FDX1L N/A 7.063176 0.00184751 CHMP2B chromatin modifying protein 2B 6.85751 1 0.03281982 calmodulin regulated spectrin-associated CAMSAP1L1 protein 1-like 1 6.801826 0.00745505 RNASEN ribonuclease type III, nuclear 6.195086 0.00604981 PRDX1 peroxiredoxin 1 6.15612 0.02465945 PHF3 PHD finger protein 3 6.1 15121 0.01437164 GCC2 GRIP and coiled-coil domain containing 2 6.081664 0.01032446 glycine cleavage system protein H GCSH (aminomethyl carrier) 6.024608 0.04401522 ZNF721 zinc finger protein 7 1 5.910076 0.01377737 Rho-associated, coiled-coil containing protein ROCK2 kinase 2 5.852909 0.03308627 BCLAF1 BCL2-associated transcription factor 1 5.819574 0.00240797 PCM1 pericentriolar material 1 5.734292 0.03714159 ubiquitin-conjugating enzyme E2D 3 UBE2D3 (UBC4/5 homolog, yeast) 5.713108 0.021 14428 CD55 molecule, decay accelerating factor for CD55 complement (Cromer blood group) 5.683509 0.00441274 COBLL1 COBL-like 1 5.653954 0.00632952 CCNG1 cyclin Gl 5.586583 0.0101 1364 GOLGA4 golgin A4 5.560977 0.02300835 PRP 8 pre-mRNA processing factor 38 PRPF38B (yeast) domain containing B 5.538255 0.01964032 DSP desmoplakin 5.501278 0.03396202 AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 5.490807 0.00483518 heterogeneous nuclear ribonucleoprotein H HNRNPH1 (H) 5.461596 0.00966327 YBX1 Y box binding protein 1 5.455093 0.00261863 NMD3 NMD3 homolog (S. cerevisiae) 5.436879 0.00447774 SLAIN2 SLAIN motif family, member 2 5.395218 0.02030348 general transcription factor IIIC, polypeptide GTF3C2 2, beta HOkDa 5.378955 0.00634443 UBAP2L ubiquitin associated protein 2-like 5.315991 0.00823742 TET3 tet oncogene family member 3 5.263592 0.01968249 SEPT11 - N/A 5.242439 0.0186971 R3HDM1 R3H domain containing 1 5.22919 0.03721685 MTDH metadherin 5.228131 0.01520368 H3F3A H3 histone, family 3A 5.188202 0.0162106 SPAST spastin 5.161775 6.01E-05 COL6A3 collagen, type VI, alpha 3 5.109395 0.02218458 PPIG peptidylprolyl isomerase G (cyclophilin G) 5.060878 0.04469338 ODC1 Ornithine decarboxylase 1 5.027819 0.0141 1638 LXN latexin 5.025051 0.00486952 RPS13 ribosomal protein S13 5.023618 0.01030916 KIAA1 143 KIAA1 143 5.017609 0.02515374 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ATP-binding cassette, sub-family A (ABC1), ABCA12 member 12 0.02867676 UBE2V1 ubiquitin-conjugating enzyme E2 variant 1 0.01282914 SNX2 sorting nexin 2 0.03586009 protein tyrosine phosphatase, non-receptor PTPN type 12 4.969861 0.02927481 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX46 46 0.03654288 NCL nucleolin 0.0056764 BZW2 basic leucine zipper and W2 domains 2 0.0016293 IGF2R insulin-like growth factor 2 receptor 0.02505894 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCA5 a, member 5 0.0187601 sema domain, immunoglobulin domain (Ig), SEMA3C short basic domain, secreted, (semaphorin) 3C 0.03498121 NOL8 nucleolar protein 8 0.02345704 eukaryotic translation elongation factor 1 EEF1AL7 alpha-like 7 0.00831902 SMC4 structural maintenance of chromosomes 4 0.03654239 MARCH 1 - N/A 0.01485637 PPIL4 peptidylprolyl isomerase (cyclophilin)-like 4 0.02987658 human immunodeficiency virus type I HIVEP1 enhancer binding protein 1 0.01033624 RPS3A ribosomal protein S3A 0.03886604 TMF1 TATA element modulatory factor 1 0.00700515 FUCA2 fucosidase, alpha-L- 2, plasma 0.03214858 LRPPRC leucine-rich PPR-motif containing 0.04328232 MDN1 MDN1, midasin homolog (yeast) 0.02424848 CAPNS1 calpain, small subunit 1 0.02265225 ZBTB45 zinc finger and BTB domain containing 45 0.00535187 TROVE2 TROVE domain family, member 2 0.00092942 Smg-7 homolog, nonsense mediated mRNA SMG7 decay factor (C. elegans) 4.490393 0.02508655 ASF1 anti-silencing function 1 homolog A (S. ASF1A cerevisiae) 0.01353041 IVNS1ABP influenza virus NS1A binding protein 0.04032226 NIPBL Nipped-B homolog (Drosophila) 0.0214311 1 Taxi (human T-cell leukemia virus type I) TAX1BP1 binding protein 1 0.00321459 PNN pinin, desmosome associated protein 0.00780293 RAP1A RAP1A, member of RAS oncogene family 0.01890408 C7orf28A chromosome 7 open reading frame 28A 0.01053364 leucine rich repeat (in FLU) interacting LRRFIP2 protein 2 0.03555186 TMEM183A transmembrane protein 183A 0.03980656 WDR64 WD repeat domain 64 0.03698108 myeloid/lymphoid or mixed-lineage leukemia MLL5 5 (trithorax homolog, Drosophila) 0.02455489 DNAJC21 DnaJ (Hsp40) homolog, subfamily C, member 0.04182551 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value 2 1 epidermal growth factor receptor pathway EPS 15 substrate 15 4.323186 0.01089252 phosphoinositide-3-kinase, regulatory subunit PIK3R3 3 (gamma) 4.285617 0.03338317 ENAH enabled homolog (Drosophila) 4.27782 0.01207197 ZMYM4 zinc finger, MYM-type 4 4.267182 0.01393137 STAG1 stromal antigen 1 4.216755 0.04048666 signal transducing adaptor molecule (SH3 STAM2 domain and ITAM motif) 2 4.170061 0.00948584 Ras association (RalGDS/AF-6) domain RASSF5 family member 5 4.1482 0.0214628 RPL37 ribosomal protein L37 4.143363 0.00991689 ZFHX3 zinc finger homeobox 3 4.10981 1 0.00434282 METTL5 methyltransferase like 5 4.101808 0.01369737 TBPL1 TBP-like 1 4.09397 0.04649146 LAPTM4A lysosomal protein transmembrane 4 alpha 4.093129 0.00222108 translocated promoter region (to activated TPR MET oncogene) 4.08363 0.00433995 biorientation of chromosomes in cell division BOD1L l-like 4.074719 0.00585576 ADAR adenosine deaminase, RNA-specific 4.052521 0.01933813 CCNI cyclin I 4.045976 0.02394342 NUP2 nucleoporin 2 OkDa 4.045013 0.004972 MINA MYC induced nuclear antigen 4.035887 0.00750673 GOLGB1 golgin B l 4.035684 0.03247406 BOLA2 bolA homolog 2 (E. coli) 4.020715 0.00624889 proteasome (prosome, macropain) 26S PSMD1 subunit, non-ATPase, 1 4.011931 0.0072001 1 bone morphogenetic protein receptor, type II BMPR2 (serine/threonine kinase) 4.01 14 0.00367358 CEP350 centrosomal protein 35OkDa 4.00531 0.01009971 ANXA4 annexin A4 3.996529 0.03274477 proteasome (prosome, macropain) 26S PSMC2 subunit, ATPase, 2 3.987502 0.00426193 HIPK1 homeodomain interacting protein kinase 1 3.965913 0.03717961 leucine-rich repeats and calponin homology LRCH3 (CH) domain containing 3 3.959914 0.03286447 DEAH (Asp-Glu-Ala-His) box polypeptide DHX15 15 3.926349 0.04456131 WRN Werner syndrome, RecQ helicase-like 3.906743 0.00075415 S stannin 3.8941 12 0.02352978 methylmalonic aciduria (cobalamin MMADHC deficiency) cblD type, with homocystinuria 3.893559 0.03029769 ZNF141 zinc finger protein 141 3.893084 0.00202819 MATR3 matrin 3 3.887861 0.03276835 RWDD4A RWD domain containing 4A 3.882013 0.02249924 6-Mar N/A 3.872003 0.03676463 SEC24D SEC24 family, member D (S. cerevisiae) 3.863242 0.01372926 TNR tenascin R (restrictin, janusin) 3.854513 0.038419 DBl/ 69437516. 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value GTPase activating Rap/RanGAP domain-like GARNL1 1 3.849157 0.00293828 DBF4 DBF4 homolog (S. cerevisiae) 3.845044 0.01450426 MOCS1 molybdenum cofactor synthesis 1 3.840436 0.03981892 ZC3H6 zinc finger CCCH-type containing 6 3.838372 0.0121 1492 HSPA1A heat shock 70kDa protein 1A 3.815485 0.03448563 NARG1 NMDA receptor regulated 1 3.802809 0.03569002 NOP58 NOP58 ribonucleoprotein homolog (yeast) 3.788493 0.00288593 EPHB4 EPH receptor B4 3.78501 1 0.02475939 RNF32 ring finger protein 32 3.769771 0.00287434 estrogen receptor binding site associated, EBAG9 antigen, 9 3.74778 0.04724541 SUPT7L suppressor of Ty 7 (S. cerevisiae)-like 3.739806 0.00867373 TRAPPC5 trafficking protein particle complex 5 3.738211 0.00696435 CCDC72 coiled-coil domain containing 72 3.729692 0.01918947 small nuclear R A activating complex, SNAPC3 polypeptide 3, 50kDa 3.710914 0.04896459 tissue factor pathway inhibitor (lipoprotein- TFPI associated coagulation inhibitor) 3.702241 0.01077594 protein kinase, cAMP-dependent, regulatory, PRKAR1A type I, alpha (tissue specific extinguisher 1) 3.700851 0.00533686 CLSPN claspin homolog (Xenopus laevis) 3.690146 0.03121386 DCTD dCMP deaminase 3.684435 0.01782176 Clorf52 chromosome 1 open reading frame 52 3.680647 0.031 17257 DPY19L4 dpy-19-like 4 (C. elegans) 3.663878 0.01007387 WAS/WASL interacting protein family, WIPF1 member 1 3.660979 0.03597595 BIRC6 baculoviral IAP repeat-containing 6 3.656537 0.01040232 OTUD4 OTU domain containing 4 3.654642 0.01272272 FIP1L1 FIP1 like 1 (S. cerevisiae) 3.647902 0.0419402 KCMF1 potassium channel modulatory factor 1 3.644039 0.00877296 UGDH UDP-glucose 6-dehydrogenase 3.642483 0.02673765 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP ATIC cyclohydrolase 3.62996 0.02012458 ANKHD1- EIF4EBP3 ANKHD1-EIF4EBP3 readthrough 3.615791 0.01331504 GPN2 GPN-loop GTPase 2 3.612946 0.00697294 Clor£21 chromosome 1 open reading frame 3.612657 0.00303055 protein phosphatase 2, regulatory subunit B, PPP2R2A alpha 3.598525 0.00122241 TLK1 tousled-like kinase 1 3.593899 0.00771066 acyl-CoA dehydrogenase, C-4 to C-12 ACADM straight chain 3.582422 0.04333075 LON peptidase N-terminal domain and ring LONRF2 finger 2 3.581772 0.0030919 Pleckstrin homology domain interacting PHIP protein 3.581619 0.02464318 myeloid/lymphoid or mixed-lineage leukemia MLL2 2 3.577065 0.00540534 B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value serine/arginine repetitive matrix 2 3.573755 0.00151055 RNA binding motif, single stranded interacting protein 1 3.573282 0.02230447 Chromosome 7 open reading frame 23 3.571619 0.01456607 ring finger and WD repeat domain 2 3.566507 0.03374643 thioredoxin domain containing 9 3.559682 0.02318797 microtubule-actin crosslinking factor 1 3.557953 0.02131704 zinc finger protein 695 3.55649 0.00881763 dihydrolipoamide dehydrogenase 3.54755 0.03042714 transcription elongation regulator 1 3.545678 0.04063693 F-box and WD repeat domain containing 3.538266 0.01890564 heat shock 70kDa protein 4 3.534902 0.02613913 ganglioside induced differentiation associated protein 2 3.533685 0.02896789 SUM01/sentrin/SMT3 specific peptidase 2 3.531085 9.19E-05 kinesin heavy chain member 2A 3.525546 0.04938074 acyl-CoA thioesterase 13 3.521514 0.0075496 guanine nucleotide binding protein-like 2 (nucleolar) 3.497915 0.01416406 polymerase (RNA) II (DNA directed) polypeptide B, 0kDa 3.486012 0.01436831 chromosome 3 open reading frame 17 3.477404 0.00064013 uracil-DNA glycosylase 3.471251 0.01530078 zinc finger protein 259 3.457681 0.04340342 eukaryotic translation initiation factor 2-alpha kinase 2 3.44408 0.03733034 Translocase of outer mitochondrial membrane 20 homolog (yeast) 3.442827 0.02955573 polymerase (RNA) II (DNA directed) polypeptide J, 13.3kDa 3.428384 0.00412324 RAN binding protein 9 3.400619 0.00125475 transcription elongation factor A (SII), 1 3.391912 0.03816125 golgi phosphoprotein 3-Iike 3.388682 0.00624767 growth differentiation factor 5 3.377286 0.00294545 Junction-mediating and regulatory protein 3.374959 0.02396428 allograft inflammatory factor 1-like 3.373096 0.0192261 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 3.368323 0.04949704 thyroid adenoma associated 3.355519 0.04286101 peptidylprolyl isomerase D 3.355162 0.01495089 myoneurin 3.346428 0.02219129 cytochrome c oxidase subunit VIIc 3.342622 0.00416541 Fas-activated serine/threonine kinase 3.341993 0.00627623 MOBl, Mps One Binder kinase activator-like B (yeast) 3.340311 0.04257654 protein phosphatase 1, regulatory (inhibitor) subunit 10 3.336889 0.01923868 epithelial cell adhesion molecule 3.323857 0.00915246 S-phase kinase-associated protein 1 3.322104 0.00151204 RAB6C, member RAS oncogene family 3.31726 0.003515 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value RNF8 ring finger protein 8 3.3143 0.00922491 THOC7 THO complex 7 homolog (Drosophila) 3.308461 0.02961408 CEP63 centrosomal protein 63kDa 3.302191 0.01209246 CENPF centromere protein F, 350/400ka (mitosin) 3.299657 0.01890505 RTN4 Reticulon 4 3.298947 0.03604368 poly (ADP-ribose) polymerase family, PARP14 member 4 3.294521 0.02209214 FNBP1L formin binding protein 1-like 3.293076 0.01994225 SDCCAG1 serologically defined colon cancer antigen 1 3.288406 0.02022995 SWI/SNF-related, matrix-associated actin- dependent regulator of chromatin, subfamily SMARCAD1 a, containing DEAD/H box 1 3.284105 0.04696085 protein kinase, AMP-activated, alpha 2 PRKAA2 catalytic subunit 3.270465 0.00135122 NCKAP1 NCK-associated protein 1 3.26989 0.00288743 PJA2 praja ring finger 2 3.267975 0.01980036 SP1 Spl transcription factor 3.262746 0.02261795 cleavage and polyadenylation specific factor CPSF3 3, 73kDa 3.262621 0.03171989 Rho-associated, coiled-coil containing protein ROCK1 kinase 1 3.257404 0.01235219 BRP44 brain protein 44 3.25371 0.00679127 SENP7 SUMOl/sentrin specific peptidase 7 3.253441 0.01090265 CDV3 CDV3 homolog (mouse) 3.247154 0.0416902 TRIM 3 tripartite motif-containing 33 3.246718 3.37E-05 SH3 domain binding glutamic acid-rich SH3BGRL protein like 3.242215 0.02599374 bromodomain adjacent to zinc finger domain, BAZ1B IB 3.237744 0.02859738 AREG amphiregulin 3.237078 0.01549385 PDCD10 programmed cell death 1 3.236064 0.00460189 ETAA1 Ewing tumor-associated antigen 1 3.231263 0.04954475 DnaJ (Hsp40) homolog, subfamily C, member DNAJC2 2 3.220929 0.01504643 EEF2 eukaryotic translation elongation factor 2 3.218901 0.03839601 DOC 7 dedicator of cytokinesis 7 3.215562 0.00207858 CAPN7 Calpain 7 3.213705 0.016063 ANAPC1 anaphase promoting complex subunit 1 3.20784 0.010159 ectonucleotide ENPP1 pyrophosphatase/phosphodiesterase 1 3.205312 0.00421566 ubiquitin-like domain containing CTD UBLCP1 phosphatase 1 3.200325 0.01796708 succinate dehydrogenase complex, subunit A, SDHA flavoprotein (Fp) 3.197073 0.01758965 nuclear pore complex interacting protein-like NPIPL3 3 3.190446 0.00688791 ZC3H13 zinc finger CCCH-type containing 13 3.190232 0.0483448 HAT1 histone acetyltransferase 1 3.188148 0.03486096 FTL ferritin, light polypeptide 3.184575 0.04393471 MAP4K3 mitogen-activated protein kinase kinase 3.183468 0.02370712 )B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value kinase kinase 3 MOBl, Mps One Binder kinase activator-like MOB L3 3 (yeast) 3.1801 17 0.01515135 SDCCAG10 Serologically defined colon cancer antigen 10 3.169853 0.00021764 ANKRD12 ankyrin repeat domain 12 3.166422 0.03652241 FLJ361 16 hypothetical locus LOC388666 3.165658 0.01949919 ZNF138 zinc finger protein 138 3.162613 0.04255118 SQLE squalene epoxidase 3.159715 0.01084816 NOL10 nucleolar protein 10 3.156696 0.04048588 SNRPE small nuclear ribonucleoprotein polypeptide E 3.155035 0.02615373 LUC7L LUC7-like (S. cerevisiae) 3.148336 0.02414327 EHBP1 EH domain binding protein 1 3.145467 0.00658037 NAMPT nicotinamide phosphoribosyltransferase 3.139672 0.002413 NARS asparaginyl-tRNA synthetase 3.134902 0.01065447 RNF14 ring finger protein 4 3.131844 0.01 179033 PFDN6 prefoldin subunit 6 3.126823 0.03269993 HMGA1 high mobility group AT-hook 1 3.126142 0.0074386 PR C protein kinase C, iota 3.1 1639 0.00319677 LASS6 LAG1 homolog, ceramide synthase 6 3.1 14282 0.02460543 C5orfl5 chromosome 5 open reading frame 15 3.104692 0.01730066 GOLIM4 golgi integral membrane protein 4 3.099776 0.03542058 ANLN anillin, actin binding protein 3.097471 0.03519748 SETD2 SET domain containing 2 3.092132 0.01030038 BAT2D1 BAT2 domain containing 1 3.08556 0.00103852 SF3B1 splicing factor 3b, subunit 1, 155kDa 3.079506 0.04359828 ERBB2IP erbb2 interacting protein 3.077623 0.01540714 DMXL1 Dmx-like 1 3.07451 0.00708549 ITPR1 inositol 1,4,5-triphosphate receptor, type 1 3.07441 0.01539608 MEMOl Mediator of cell motility 1 3.070708 0.01237261 AKD2 N/A 3.069178 0.01556957 HIBCH 3-hydroxyisobutyryl-CoA hydrolase 3.065273 0.01688263 SOS1 son of sevenless homolog 1 (Drosophila) 3.063455 0.01573618 S100A1 S 00 calcium binding protein A 3.056371 0.02159673 guanine nucleotide binding protein (G GNB1 protein), beta polypeptide 1 3.050983 0.02355176 CASQ1 calsequestrin 1 (fast-twitch, skeletal muscle) 3.045838 0.01434468 CYCS cytochrome c, somatic 3.041 128 0.04095219 SP3 Sp3 transcription factor 3.033516 0.00452105 ZNF107 Zinc finger protein 107 3.029659 0.00307174 INPP5F inositol polyphosphate-5 -phosphatase F 3.026291 0.04307517 La ribonucleoprotein domain family, member LARP7 7 3.023688 0.02499879 RERE arginine-glutamic acid dipeptide (RE) repeats 3.021721 0.00650595 ubiquitin protein ligase E3 component n- UBR4 recognin 4 3.010769 0.01930641 ZFR zinc finger RNA binding protein 3.008818 0.04831955 SFRS18 splicing factor, arginine/serine-rich 18 2.999356 0.00938084 HPS3 Hermansky-Pudlak syndrome 3 2.997907 0.03836478 DPYD dihydropyrimidine dehydrogenase 2.997333 0.000671 1 ITGB6 integrin, beta 6 2.989866 0.03976203 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CSRNP3 cysteine-serine-rich nuclear protein 3 0.00956 MORF4L2 mortality factor 4 like 2 0.03027653 ZMYM6 zinc finger, MYM-type 6 0.04641004 mutS homolog 2, colon cancer, nonpolyposis MSH2 type 1 (E. coli) 0.03627096 PRMT6 protein arginine methyltransferase 6 0.02512139 TTC3 tetratricopeptide repeat domain 3 0.01436294 activating signal cointegrator 1 complex ASCC3 subunit 3 0.00589593 RAD54L2 RAD54-like 2 (S. cerevisiae) 0.02651723 TP63 tumor protein p63 0.02945318 ZNF273 zinc finger protein 273 0.0417131 PUM2 pumilio homolog 2 (Drosophila) 0.02935277 CCNC cyclin C 0.00690543 ENY2 enhancer of yellow 2 homolog (Drosophila) 0.00070793 MRPL53 mitochondrial ribosomal protein L53 0.03432129 transient receptor potential cation channel, TRPM6 subfamily M, member 6 2.939987 0.01854453 SMT3 suppressor of mif two 3 homolog 1 (S. SUMOl cerevisiae) 0.01314778 EPM2AIP1 EPM2A (laforin) interacting protein 1 0.01328695 solute carrier family 9 (sodium/hydrogen SLC9A1 exchanger), member 1 0.01354005 DNA cross-link repair B (PS02 homolog, S. DCLRE1B cerevisiae) 0.02550563 bromodomain adjacent to zinc finger domain, BAZ2B 2B 0.02326191 ZC3H15 zinc finger CCCH-type containing 15 0.00317773 FERMT2 fermitin family homolog 2 (Drosophila) 0.00196358 SENP6 SUMOl/sentrin specific peptidase 6 0.01329545 SPOPL speckle-type POZ protein-like 0.03963368 ARMC10 armadillo repeat containing 10 0.03572479 ALCAM activated leukocyte cell adhesion molecule 0.03361215 IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 0.02633645 PLS1 plastin 1 0.02158573 REEP5 receptor accessory protein 5 0.00852534 Clorfll2 chromosome 1 open reading frame 112 0.02221652 Histidine acid phosphatase domain containing HISPPD1 1 2.912902 0.04467233 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 7 (GalNAc- GALNT7 T7) 0.00233517 CRYGS crystallin, gamma S 0.01223416 BRAP BRCA1 associated protein 0.00707534 TCP1 t-complex 1 0.02939434 heterogeneous nuclear ribonucleoprotein U HNRNPU (scaffold attachment factor A) 0.01266994 C7orf36 chromosome 7 open reading frame 36 0.00731727 RBBP6 retinoblastoma binding protein 6 0.03577545 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value malic enzyme 2, NAD(+)-dependent, ME2 mitochondrial 2.886661 0.01 12677 ARID4A AT rich interactive domain 4A (RBPl-like) 2.882351 0.00235678 malic enzyme 1, NADP(+)-dependent, ME1 cytosolic 2.879955 0.00454168 CDC2L6 Cell division cycle 2-like 6 (CDK8-like) 2.879457 0.04351 182 DST dystonin 2.875358 0.04305397 MY018A myosin XVIIIA 2.875272 0.01734509 USP39 ubiquitin specific peptidase 39 2.866674 0.00731577 OSBPL1 1 oxysterol binding protein-like 11 2.865043 0.00441915 LTV1 LTV1 homolog (S. cerevisiae) 2.862159 0.03848354 MGC5590 hypothetical protein MGC5590 2.858516 0.00173223 BAIAP2L1 BAI1 -associated protein 2-like 1 2.85848 0.02297787 GREB1 GREB1 protein 2.856279 0.03013008 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCC1 c, member 1 2.85378 0.03745351 signal transducer and activator of STAT1 transcription 1, 91kDa 2.849821 0.01959205 ubiquitin specific peptidase 13 (isopeptidase USP13 T-3) 2.848679 0.03625006 SASS6 spindle assembly 6 homolog (C. elegans) 2.845356 0.02224778 ZNF71 1 zinc finger protein 7 1 2.844816 0.02480081 SOX4 SRY (sex determining region Y)-box 4 2.841366 0.04188377 inturned planar cell polarity effector homolog INTU (Drosophila) 2.839753 0.00781462 CCDC99 coiled-coil domain containing 99 2.834983 0.04509615 ZNF644 zinc finger protein 644 2.83475 0.02847176 UDP-GlcNAc:betaGal beta-l,3-N- B3GNT2 acetylglucosaminyltransferase 2 2.830064 0.0205201 SMC3 structural maintenance of chromosomes 3 2.825491 0.03046467 TOP2B topoisomerase (DNA) II beta 180kDa 2.823094 0.02218412 FDFT1 farnesyl-diphosphate farnesyltransferase 1 2.822416 0.00648518 TBL1XR1 transducin (beta)-like 1 X-linked receptor 1 2.821702 0.01803827 RBAK RB-associated KRAB zinc finger 2.818775 0.04331016 TTLL5 tubulin tyrosine ligase-like family, member 5 2.815279 0.01605047 MLPH melanophilin 2.814576 0.02628659 DnaJ (Hsp40) homolog, subfamily B, member DNAJB1 11 2.813687 0.01 128434 WWC1 WW and C2 domain containing 1 2.813524 0.00083617 ZNF91 zinc finger protein 9 2.81138 0.02662892 ATPase, H+ transporting, lysosomal 70kDa, ATP6V1A VI subunit A 2.81 115 0.00180419 KIAA0746 KIAA0746 protein 2.80153 0.00643297 ArfGAP with SH3 domain, ankyrin repeat ASAP1 and PH domain 1 2.799124 0.00462787 ANKHD1 ankyrin repeat and KH domain containing 1 2.79893 0.02854279 family with sequence similarity 184, member FAM184A A 2.798923 0.00430328 HLTF helicase-like transcription factor 2.797219 0.02779826 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value Eukaryotic translation initiation factor 2A, EIF2A 65kDa 2.797166 0.03413535 cyclin D binding myb-like transcription factor DMTF1 1 2.794307 0.0338541 GPR125 G protein-coupled receptor 125 2.788845 0.04717651 RPL4 ribosomal protein L4 2.783907 0.03613678 YTHDC2 YTH domain containing 2 2.783345 0.00761701 growth arrest and DNA-damage-inducible, GADD45A alpha 2.781856 0.04855598 USP34 ubiquitin specific peptidase 34 2.781149 0.03969944 family with sequence similarity 92, member FAM92A1 Al 2.779772 0.00652292 GLA galactosidase, alpha 2.779352 0.00885348 SMC6 structural maintenance of chromosomes 6 2.772324 0.01058738 SKIL SKI-like oncogene 2.76743 0.01 121972 SEC24A SEC24 family, member A (S. cerevisiae) 2.766295 0.0030784 minichromosome maintenance complex MCM4 component 4 2.764255 0.01639846 RAS p21 protein activator (GTPase activating RASA1 protein) 1 2.760016 0.02594615 v-ral simian leukemia viral oncogene RALA homolog A (ras related) 2.759055 0.01615779 IWS1 IWS1 homolog (S. cerevisiae) 2.757355 0.01397659 ITSN2 intersectin 2 2.754509 0.03995086 nuclear undecaprenyl pyrophosphate synthase NUS1 1 homolog (S. cerevisiae) 2.753898 0.02727482 CENPE centromere protein E, 3 12kDa 2.7536 0.0165937 COL7A1 collagen, type VII, alpha 1 2.753254 0.01516653 TTC17 tetratricopeptide repeat domain 17 2.750758 0.01252676 nuclear casein kinase and cyclin-dependent NUCKS1 kinase substrate 1 2.746242 0.01149953 EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242 C6orf203 chromosome 6 open reading frame 203 2.739947 0.02384998 chaperonin containing TCP1, subunit 5 CCT5 (epsilon) 2.739476 0.00602847 TPP1 tripeptidyl peptidase I 2.737982 0.01551944 GPR160 G protein-coupled receptor 160 2.733023 0.01181892 CCAAT/enhancer binding protein (C/EBP), CEBPZ zeta 2.730668 0.04807979 SGOL1 shugoshin-like 1 (S. pombe) 2.730587 0.02367326 AFF1 AF4/FMR2 family, member 1 2.728118 0.01644025 Ras association (RalGDS/AF-6) and RAPH1 pleckstrin homology domains 1 2.723734 0.01713881 NMBR neuromedin B receptor 2.7228 0.04557912 speedy homolog E8 (Xenopus laevis), SPDYE8P pseudogene 2.721673 0.04081118 FLNB filamin B, beta 2.718523 0.02624732 RAD18 RAD 18 homolog (S. cerevisiae) 2.717404 0.03339343 ZNF595 zinc finger protein 595 2.717382 0.01742071 SFRS3 splicing factor, arginine/serine-rich 3 2.716461 0.03522487 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ARID IB AT rich interactive domain IB (SWIl-Iike) 2.716295 0.01486205 NOMOl NODAL modulator 1 2.71502 0.03140578 DEPDC6 DEP domain containing 6 2.714996 0.04184413 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX39 39 2.714312 0.0446041 1 HIST2H2AC histone cluster 2, H2ac 2.712756 0.04657073 tRNA-yW synthesizing protein 3 homolog (S. TYW3 cerevisiae) 2.711091 0.01835147 RBM47 RNA binding motif protein 47 2.709999 0.00456872 SC4MOL sterol-C4-methyl oxidase-like 2.708706 0.00099333 RWDD1 RWD domain containing 1 2.70643 0.03976333 PSIP1 PC4 and SFRS1 interacting protein 1 2.704173 0.00379656 NPNT nephronectin 2.690413 0.03429433 ZNHIT6 zinc finger, HIT type 6 2.688391 0.00045453 PPIC peptidylprolyl isomerase C (cyclophilin C) 2.684486 0.01273313 MRPS30 mitochondrial ribosomal protein S30 2.676295 0.02689152 RAB10 RAB10, member RAS oncogene family 2.675383 0.00826866 ATPase, H+ transporting, lysosomal 42kDa, ATP6V1C1 V I subunit C 2.667986 0.01481745 ATPase, H+ transporting, lysosomal 31kDa, ATP6V1E1 V subunit El 2.666607 0.02899272 polymerase (RNA) mitochondrial (DNA POLRMT directed) 2.662838 0.0274167 EPRS glutamyl-prolyl-tRNA synthetase 2.662763 0.04513234 GPBP1L1 GC-rich promoter binding protein 1-like 1 2.662573 0.04921046 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX18 8 2.65979 0.0499591 1 TOPBP1 topoisomerase (DNA) II binding protein 1 2.659609 0.01512887 C7orf70 chromosome 7 open reading frame 70 2.658797 0.01611322 SMC5 structural maintenance of chromosomes 5 2.657527 0.031 10443 ZNF267 zinc finger protein 267 2.656681 0.02959774 sterile alpha motif and leucine zipper ZAK containing kinase AZK 2.652971 0.01651627 PRLR prolactin receptor 2.652089 0.01578686 KIFAP3 kinesin-associated protein 3 2.651664 0.01016367 FOX03 forkhead box 0 3 2.649989 0.022331 2 eukaryotic translation initiation factor 2, EIF2S2 subunit 2 beta, 38kDa 2.64701 0.04577479 excision repair cross-complementing rodent ERCC5 repair deficiency, complementation group 5 2.64652 0.03234078 DLG1 discs, large homolog 1 (Drosophila) 2.644522 0.02181855 cell division cycle 2-like 2 (PITSLRE CDC2L2 proteins) 2.640105 0.02399518 ZNF326 Zinc finger protein 326 2.639598 0.00776776 WDR60 WD repeat domain 60 2.639518 0.03968372 translocase of inner mitochondrial membrane TIMM17A 17 homolog A (yeast) 2.638869 0.01019151 HDAC4 histone deacetylase 4 2.63716 0.04572722 GLS glutaminase 2.631911 0.03419736 NOTCH2NL Notch homolog 2 (Drosophila) N-terminal 2.630848 0.01387699 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value like OPA1 optic atrophy 1 (autosomal dominant) 2.629144 0.00144393 SYN1 synapsin I 2.625746 0.00855739 DnaJ (Hsp40) homolog, subfamily B, member DNAJB14 14 2.625377 0.00031245 MBNL1 muscleblind-like (Drosophila) 2.616546 0.03413969 NUP155 nucleoporin 155kDa 2.614158 0.025106 7-Mar N/A 2.613053 0.01914936 C6orf97 chromosome 6 open reading frame 97 2.612996 0.01980769 HOOK2 hook homolog 2 (Drosophila) 2.611427 0.03199086 CCDC90A coiled-coil domain containing 90A 2.609805 0.02466542 PHC3 polyhomeotic homolog 3 (Drosophila) 2.608236 0.01227659 cell division cycle 73, Pafl/RNA polymerase II complex component, homolog (S. CDC73 cerevisiae) 2.602783 0.02198234 DAXX death-domain associated protein 2.601609 0.0097589 SF3B5 splicing factor 3b, subunit 5, lOkDa 2.593595 0.01024026 ANKRD17 ankyrin repeat domain 1 2.592918 0.00227678 ARF4 ADP-ribosylation factor 4 2.58944 0.01239217 HTT huntingtin 2.588494 0.04753706 FER fer (fps/fes related) tyrosine kinase 2.588405 0.03773494 SNX4 sorting nexin 4 2.588041 0.04103538 protein phosphatase 2, regulatory subunit B, PPP2R2C gamma 2.586023 0.01065025 OLA1 Obg-like ATPase 1 2.585883 0.00413626 Clorfl35 chromosome 1 open reading frame 135 2.585302 0.03438371 RNF216 ring finger protein 216 2.584577 0.01318104 far upstream element (FUSE) binding protein FUBP1 1 2.584276 0.02883731 WDFY1 WD repeat and FYVE domain containing 1 2.584271 0.02398677 minichromosome maintenance complex MCM3AP component 3 associated protein 2.583767 0.01780226 TRAF family member-associated NFKB TANK activator 2.583302 0.02722171 ACBD3 acyl-CoA binding domain containing 3 2.576254 0.02388443 THBS3 thrombospondin 3 2.575883 0.01390215 CXXC5 CXXC finger 5 2.57271 0.01699583 CSNK1A1 casein kinase 1, alpha 1 2.565332 0.02008984 YTHDC1 YTH domain containing 1 2.564672 0.04083437 B double prime 1, subunit of R A polymerase III transcription initiation factor BDP1 IIIB 2.563562 0.0098413 catenin (cadherin-associated protein), alpha , CTNNA1 102kDa 2.563386 0.01924656 PHF14 PHD finger protein 14 2.562435 0.00856813 YEATS2 YEATS domain containing 2 2.561844 0.03698105 ribosomal RNA processing 15 homolog (S. RRP15 cerevisiae) 2.558002 0.00434063 REV3-like, catalytic subunit of D A REV3L polymerase zeta (yeast) 2.557663 0.00922597 DBl/ 69437516. 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SRP72 signal recognition particle 72kDa 2.557519 0.02100872 PKP4 plakophilin 4 2.557151 0.00914 DCN1, defective in cullin neddylation 1, DCUN1D4 domain containing 4 (S. cerevisiae) 2.556521 0.02739626 caspase 2, apoptosis-related cysteine CASP2 peptidase 2.555916 0.0459927 UTRN utrophin 2.55405 0.00844229 BAT2 HLA-B associated transcript 2 2.553422 0.02006314 polymerase (RNA) II (DNA directed) POLR2J2 polypeptide J2 2.550879 0.00054071 CLGN calmegin 2.549584 0.0097492 FAM45B family with sequence similarity 45, member B 2.546071 0.0026172 SF S5 splicing factor, arginine/serine-rich 5 2.545075 0.02950629 TIP41, TOR signaling pathway regulator-like TIPRL (S. cerevisiae) 2.541724 0.03186236 C3orf57 chromosome 3 open reading frame 57 2.540082 0.0094237 RNGTT RNA guanylyltransferase and 5'-phosphatase 2.538319 0.03659254 USP46 ubiquitin specific peptidase 46 2.536854 0.0195821 1 DDX1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 1 2.534563 0.00605707 proteasome (prosome, macropain) 26S PSMD14 subunit, non-ATPase, 14 2.533865 0.02390241 KRIT1 KRIT1, ankyrin repeat containing 2.533715 0.00341833 GULP, engulfment adaptor PTB domain GULP1 containing 1 2.53321 1 0.00031662 ubiquitin protein ligase E3 component n- UBR2 recognin 2 2.5291 12 0.02522009 CLK4 CDC-like kinase 4 2.519794 0.04344857 protein phosphatase 2, regulatory subunit B', PPP2R5C gamma 2.51958 0.01802986 NOTCH3 Notch homolog 3 (Drosophila) 2.518418 0.02050312 CUL3 cullin 3 2.512555 0.03000904 KLHL20 kelch-like 20 (Drosophila) 2.511604 0.04625872 PLK4 polo-like kinase 4 (Drosophila) 2.510571 0.02626713 v-raf-1 murine leukemia viral oncogene RAF1 homolog 1 2.510375 0.04663954 CD2AP CD2-associated protein 2.509456 0.04171078 HSF2 heat shock transcription factor 2 2.506697 0.02377126 family with sequence similarity 98, member FAM98A A 2.506122 0.01 113668 BTF3 basic transcription factor 3 2.504564 0.04945883 TLN2 talin 2 2.504179 0.01450135 ANKRD36B ankyrin repeat domain 36B 2.501792 0.01895399 ACTR3 ARP3 actin-related protein 3 homolog (yeast) 2.500061 0.02540777 MOB 1, Mps One Binder kinase activator-like MOBKL1A 1A (yeast) 2.495315 0.01061014 DEAD (Asp-Glu- Ala-Asp) box polypeptide DDX55 55 2.494592 0.02799053 TRIP12 thyroid hormone receptor interactor 12 2.494017 0.03689934 ARID4B AT rich interactive domain 4B (RBPl-like) 2.49337 0.03529843 NLN neurolysin (metallopeptidase M3 family) 2.492964 0.01595546 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P value USP3 ubiquitin specific peptidase 3 2.491308 0.03275649 MBD4 methyl-CpG binding domain protein 4 2.48954 0.01907074 pituitary tumor-transforming 1 interacting PTTG1IP protein 2.486349 0.0297117 brain and reproductive organ-expressed BRE (TNFRSF1A modulator) 2.484356 0.00442756 KDM1 N/A 2.481278 0.00750192 QSER1 glutamine and serine rich 1 2.475907 0.0242896 MRPL18 Mitochondrial ribosomal protein L 8 2.474773 0.01902557 glycerol-3-phosphate dehydrogenase 2 GPD2 (mitochondrial) 2.471884 0.03872717 PHACTR2 phosphatase and actin regulator 2 2.470462 0.01247884 protein phosphatase 1, catalytic subunit, beta PPP1CB isozyme 2.468217 0.04691501 BCL9 B-cell CLL/lymphoma 9 2.457588 0.01401656 recombination signal binding protein for RBPJ immunoglobulin kappa J region 2.456823 0.03872586 Transient receptor potential cation channel, TRPM8 subfamily M, member 8 2.455114 0.00945206 RSBN1 round spermatid basic protein 1 2.453006 0.00130387 USP33 ubiquitin specific peptidase 33 2.452053 0.01813434 NEB nebulin 2.449909 0.03071673 CTAGE5 CTAGE family, member 5 2.447423 0.03469659 GPBP1 GC-rich promoter binding protein 1 2.445774 0.03848269 AZI2 5-azacytidine induced 2 2.445213 0.03482439 tRNA-yW synthesizing protein 1 homolog (S. TYW1 cerevisiae) 2.445006 0.0446882 FOXJ3 forkhead box J3 2.441988 0.01508939 BXDC5 Brix domain containing 5 2.437638 0.01014076 SGOL2 shugoshin-like 2 (S. pombe) 2.436637 0.00564431 PTPRF interacting protein, binding protein 1 PPFIBP1 (liprin beta 1) 2.431492 0.03837188 melanoma inhibitory activity family, member MIA3 3 2.431448 0.03171622 SDC2 syndecan 2 2.42999 0.04326632 WHSC1 Wolf-Hirschhorn syndrome candidate 1 2.429055 0.01584686 LRRC16A leucine rich repeat containing 16A 2.428642 0.00030284 TMEM106B transmembrane protein 106B 2.426336 0.00185522 SATB2 SATB homeobox 2 2.426291 0.00519515 CLIC4 chloride intracellular channel 4 2.420927 0.04525662 ARMC8 armadillo repeat containing 8 2.420129 0.02913344 USP48 ubiquitin specific peptidase 48 2.418434 0.03846682 RSRC2 arginine/serine-rich coiled-coil 2 2.415397 0.0414388 RNF149 ring finger protein 149 2.415338 0.00678303 CDCA2 Cell division cycle associated 2 2.414986 0.04014665 Split hand/foot malformation (ectrodactyly) SHFM1 type 1 2.411671 0.02417581 ENOPH1 enolase-phosphatase 1 2.411171 0.01301109 PFN2 profilin 2 2.410395 0.008569 RDBP RD RNA binding protein 2.410004 0.01 193128 / 694375 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value TACSTD2 tumor-associated calcium signal transducer 2 2.409326 0.03705571 WW domain containing E3 ubiquitin protein W P1 ligase 1 2.407783 0.01240765 TAGLN2 transgelin 2 2.407305 0.03670214 COPG coatomer protein complex, subunit gamma 2.406812 0.03959455 nucleophosmin (nucleolar phosphoprotein NPM1 B23, numatrin) 2.406641 0.01665033 UDP-glucose ceramide glucosyltransferase- UGCGL1 like 1 2.402575 0.00193798 hexose-6-phosphate dehydrogenase (glucose H6PD 1-dehydrogenase) 2.401089 0.037271 15 myeloid/lymphoid or mixed-lineage leukemia MLL3 3 2.397088 0.00923063 SEC63 SEC63 homolog (S. cerevisiae) 2.3961 0.00304391 E74-like factor 2 (ets domain transcription ELF2 factor) 2.39587 0.00551064 eukaryotic translation elongation factor 1 EEF1E1 epsilon 1 2.394143 0.01844291 CREG1 cellular repressor of ElA-stimulated genes 1 2.392246 0.02861787 KIAA0922 KIAA0922 2.388858 0.0279595 CLIPl CAP-GLY domain containing linker protein 1 2.384416 0.03137165 FAM3C family with sequence similarity 3, member C 2.383435 0.00661523 CCNL1 Cyclin LI 2.383196 0.03715368 HHLA3 HERV-H LTR-associating 3 2.381252 0.04036587 nascent-polypeptide-associated complex NACAPI alpha polypeptide pseudogene 1 2.380781 0.03679794 C2orf49 chromosome 2 open reading frame 49 2.380543 0.03557126 SDC3 Syndecan 3 2.377861 0.01536423 C7orf30 chromosome 7 open reading frame 30 2.375592 0.00732418 C7orf60 chromosome 7 open reading frame 60 2.375581 0.0051832 RAB1A RAB1 A, member RAS oncogene family 2.373609 0.04191459 TOPORS Topoisomerase I binding, arginine/serine-rich 2.371666 0.03979896 DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9 2.370434 0.0025908 RHBDF2 rhomboid 5 homolog 2 (Drosophila) 2.366587 0.03932245 low density lipoprotein receptor-related LRP1 protein 1 2.365807 0.00104357 ATPase, Ca++ transporting, type 2C, member ATP2C1 1 2.36579 0.00861049 EXOSC10 exosome component 10 2.36316 0.0220261 ZBTB11 zinc finger and BTB domain containing 11 2.362742 0.01423144 DMKN dermokine 2.360421 0.03954072 USOl vesicle docking protein homolog USOl (yeast) 2.359821 0.02226331 AHCTF1 AT hook containing transcription factor 1 2.359072 0.00613172 INTS4 integrator complex subunit 4 2.358132 0.03508975 RIOK1 RIO kinase 1 (yeast) 2.354234 0.01010178 metal response element binding transcription MTF2 factor 2 2.354146 0.0214147 poly (ADP-ribose) polymerase family, PARP8 member 8 2.353916 0.02193377 1/ 69437516.1 Supplemental Tabic 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value C3orf49 chromosome 3 open reading frame 49 2.35178 0.0201645 glutaminyl-tRNA synthase (glutamine- QRSL1 hydrolyzing)-like 1 2.349048 0.02832035 V-myc myelocytomatosis viral oncogene MYC homolog (avian) 2.348995 0.02396725 ZBTB41 zinc finger and BTB domain containing 4 1 2.345229 0.04085399 procollagen-lysine, 2-oxoglutarate 5- PLOD2 dioxygenase 2 2.345036 0.0201 1477 family with sequence similarity 119, member FAM1 19A A 2.33913 0.0058591 KIF2C kinesin family member 2C 2.338823 0.02722488 RAB7A RAB7A, member RAS oncogene family 2.338591 0.00328242 NSU 5 NOP2/Sun domain family, member 5 2.337845 0.03644286 CD46 molecule, complement regulatory CD46 protein 2.333239 0.02096143 CEP135 centrosomal protein 135kDa 2.333179 0.01103042 thioredoxin domain containing 5 TXNDC5 (endoplasmic reticulum) 2.332472 0.00547594 Leol, Pafl/RNA polymerase II complex LEOl component, homolog (S. cerevisiae) 2.332126 0.02737226 WDSOF1 WD repeats and SOF1 domain containing 2.33082 0.00345726 CTBS chitobiase, di-N-acetyl- 2.330361 0.02094886 CEP 170 centrosomal protein 170kDa 2.328966 0.0312379 AK2 adenylate kinase 2 2.32623 0.04153099 ERRFIl ERBB receptor feedback inhibitor 1 2.325127 0.01808355 MREG melanoregulin 2.32298 0.02918713 ZNF184 zinc finger protein 84 2.320743 0.03883664 CHMP4C chromatin modifying protein 4C 2.319309 0.0139899 ZFYVE9 zinc finger, FYVE domain containing 9 2.318986 0.00076831 WDR34 WD repeat domain 34 2.318692 0.03570756 protein tyrosine phosphatase, non-receptor type 13 (APO-1/CD95 (Fas)-associated ΡΤΡΝ Ϊ 3 phosphatase) 2.316902 0.03008615 SH3-domain binding protein 5 (BTK- SH3BP5 associated) 2.315352 0.00347119 RHOB ras homolog gene family, member B 2.314938 0.00360295 polycystic kidney disease 2 (autosomal PKD2 dominant) 2.312196 0.00272198 eukaryotic translation initiation factor 4 EIF4G3 gamma, 3 2.31 1806 0.03563678 protein tyrosine phosphatase, non-receptor PTPN22 type 22 (lymphoid) 2.310831 0.03701475 UBE2C ubiquitin-conjugating enzyme E2C 2.309809 0.03275616 ATP-binding cassette, sub-family F (GCN20), ABCF1 member 1 2.309064 0.04908242 acyl-CoA synthetase long-chain family ACSL3 member 3 2.306145 0.01677941 GPR126 G protein-coupled receptor 1 6 2.302486 0.01624519 RUFY1 RUN and FYVE domain containing 1 2.302149 0.00032141 RCC2 regulator of chromosome condensation 2 2.300055 0.04480846 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value MRPL3 mitochondrial ribosomal protein L3 2.298195 0.03084317 BXDC1 Brix domain containing 1 2.297265 0.02647709 PCBP4 poly(rC) binding protein 4 2.297239 0.0480034 FKBP3 FK506 binding protein 3, 25kDa 2.294143 0.00750185 CRELD1 cysteine-rich with EGF-like domains 1 2.292013 0.01054939 IMMT inner membrane protein, mitochondrial 2.291678 0.02551435 TRBC2 T cell receptor beta constant 2 2.291039 0.01815739 ABI2 abl-interactor 2 2.29011 1 0.04912702 Phosphatidylinositol 4-kinase, catalytic, alpha PI4KAP2 pseudogene 2 2.287821 0.01409133 FYTTD1 forty-two-three domain containing 1 2.286731 0.02369016 THEM4 thioesterase superfamily member 4 2.286356 0.042979 ZNF638 zinc finger protein 638 2.285398 0.02130371 SLC25A46 solute carrier family 25, member 46 2.284449 0.00388639 LR C9 N/A 2.28276 0.00475323 establishment of cohesion 1 homolog 1 (S. ESCOl cerevisiae) 2.280783 0.02158678 chromodomain helicase DNA binding protein CHD1 1 2.27918 0.02465009 protein phosphatase 1, regulatory (inhibitor) PPP1R12A subunit 12A 2.277063 0.04329455 PTPRK protein tyrosine phosphatase, receptor type, K 2.273966 0.01124848 ACVR1 activin A receptor, type I 2.273641 0.00180738 SFRS12 splicing factor, arginine/serine-rich 12 2.271856 0.01864358 protein tyrosine phosphatase type IVA, PTP4A1 member 1 2.270167 0.00847749 transforming, acidic coiled-coil containing TACC3 protein 3 2.268162 0.01045492 general transcription factor IIH, polypeptide GTF2H2 2, 44kDa 2.267553 0.04759197 FK506 binding protein 12-rapamycin FRAP1 associated protein 1 2.265502 0.01 17058 SF3B2 splicing factor 3b, subunit 2, 145kDa 2.264361 0.01 19544 RPTOR independent companion of MTOR, RICTOR complex 2 2.26423 0.02269076 RNF115 ring finger protein 15 2.263794 0.0345823 TCEA3 transcription elongation factor A (SII), 3 2.261769 0.00150668 RNF168 ring finger protein 168 2.260016 0.02333929 transient receptor potential cation channel, TRPM5 subfamily M, member 5 2.259096 0.00420324 7-Sep N/A 2.256637 0.0285657 JARID2 jumonji, AT rich interactive domain 2 2.254895 0.01620599 nuclear receptor subfamily 1, group D, NR1D2 member 2 2.254522 0.03475131 general transcription factor IIIC, polypeptide GTF3C6 6, alpha 35kDa 2.249268 0.04271905 pleckstrin homology domain containing, PLEKHF2 family F (with FYVE domain) member 2 2.24915 0.03034525 CDC42 binding protein kinase alpha (DMPK- CDC42BPA like) 2.24623 0.00937014 1/69437516.1 Supplemental Table 1. Gene Transcripts Upregulatcd by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value PACRGL PARK2 co-regulated-like 2.24344 0.01 105086 BTF3L4 basic transcription factor 3-like 4 2.243375 0.03396626 MTX1 metaxin 1 2.240865 0.04610751 PRP40 pre-mRNA processing factor 40 PRPF40A homolog A (S. cerevisiae) 2.237862 0.03098713 TBC1 (tre-2/USP6, BUB2, cdcl6) domain TBC1D1 family, member 1 2.235136 0.00238682 TBC1D14 TBC1 domain family, member 14 2.23396 0.00059499 solute carrier family 6 (neurotransmitter SLC6A6 transporter, taurine), member 6 2.233084 0.01778543 ATPase, Na+/K+ transporting, alpha 1 ATP1A1 polypeptide 2.231444 0.0033896 PANK4 pantothenate kinase 4 2.230306 0.01598754 MYEOV2 myeloma overexpressed 2 2.229539 0.048704 DEPDC1 DEP domain containing 1 2.22899 0.03843419 La ribonucleoprotein domain family, member LARP2 2 2.228433 0.01018392 mitogen-activated protein kinase kinase MAP3K6 kinase 6 2.227417 0.03751421 chaperonin containing TCP1, subunit 6A CCT6A (zeta 1) 2.226682 0.02645749 golgi-associated PDZ and coiled-coil motif GOPC containing 2.226256 0.03894013 SCARB2 scavenger receptor class B, member 2 2.225542 0.00468326 KPNA1 karyopherin alpha 1 (importin alpha 5) 2.225491 0.02352899 KIAA1967 KIAA1967 2.224672 0.00664399 RANBP2 RAN binding protein 2 2.224515 0.03771 105 C6orfl06 chromosome 6 open reading frame 106 2.223548 0.03053372 JTB jumping translocation breakpoint 2.221965 0.01933583 oxidoreductase NAD-binding domain OXNAD1 containing 1 2.217194 0.04995544 C2orf3 chromosome 2 open reading frame 3 2.214359 0.03959238 DARS2 aspartyl-tRNA synthetase 2, mitochondrial 2.213768 0.02672262 FBX09 F-box protein 9 2.212575 0.00029593 HNR PK heterogeneous nuclear ribonucleoprotein K 2.212481 0.01145842 KIF15 kinesin family member 15 2.211394 0.04216057 ATR ataxia telangiectasia and Rad3 related 2.210707 0.03297327 ZC3H11A zinc finger CCCH-type containing 11A 2.210603 0.01108381 SYCP2L synaptonemal complex protein 2-like 2.21008 0.02356155 STK10 serine/threonine kinase 10 2.209612 0.01624999 DEAH (Asp-Glu-Ala-His) box polypeptide DHX36 36 2.209532 0.01561221 small nuclear ribonucleoprotein polypeptide SNRPG G 2.208125 0.01762589 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCC2 c, member 2 2.20742 0.04232519 hyaluronan-mediated motility receptor MMR (RHAMM) 2.206968 0.02153581 TRRAP transformation/transcription domain- 2.204836 0.00948173 B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value associated protein USP1 ubiquitin specific peptidase 1 2.204293 0.02425862 3-hydroxy-3-methylglutaryl-CoA synthase 1 HMGCS1 (soluble) 2.202971 0.04764687 LanC lantibiotic synthetase component C-like LANCL3 3 (bacterial) 2.202319 0.01353871 PPIE peptidylprolyl isomerase E (cyclophilin E) 2.202103 0.0337451 1 ADP-ribosylation factor guanine nucleotide- ARFGEF1 exchange factor l(brefeldin A-inhibited) 2.200694 0.03552716 CCDC104 coiled-coil domain containing 104 2.200303 0.0341 1197 STT3, subunit of the oligosaccharyltransferase complex, homolog STT3B B (S. cerevisiae) 2.199036 0.03541682 ITNRNPR heterogeneous nuclear ribonucleoprotein R 2.197778 0.04812168 SFRS1 1 splicing factor, arginine/serine-rich 11 2.197102 0.03128218 ZNF281 zinc finger protein 281 2.19509 0.01743985 EXOC1 exocyst complex component 1 2.193714 0.01664327 GTF2I general transcription factor i 2.193136 0.01310569 mutL homolog 1, colon cancer, nonpolyposis MLH1 type 2 (E. coli) 2.1927 0.00460208 2-Sep N/A 2.191638 0.04509541 R F4 ring finger protein 4 2.190935 0.04556102 BCL2/adenovirus E1B 19kDa interacting BNIP3L protein 3-like 2.190636 0.02883592 ubiquitin-conjugating enzyme E2K (UBC1 UBE2K homolog, yeast) 2.187646 0.04056877 COG5 component of oligomeric golgi complex 5 2.18755 0.01867518 LAMC1 laminin, gamma 1 (formerly LAMB2) 2.186259 0.01464433 suppressor of defective silencing 3 homolog SUDS3 (S. cerevisiae) 2.184154 0.02450571 TMEM70 transmembrane protein 70 2.18302 0.01154643 SMYD2 SET and MYND domain containing 2 2.182951 0.03899734 LHB luteinizing hormone beta polypeptide 2.182615 0.01722195 TMEM173 transmembrane protein 173 2.180848 0.03326728 v-myb myeloblastosis viral oncogene MYB homolog (avian) 2.180272 0.03642402 WR IP1 Werner helicase interacting protein 1 2.178547 0.0355725 UDP glucuronosyltransferase 1 family, UGT1A1 polypeptide Al 2.177598 0.02829903 HSPA1L heat shock 70kDa protein 1-like 2.176998 0.0201304 MAK16 MAK16 homolog (S. cerevisiae) 2.173803 0.00414123 N-acyl phosphatidylethanolamine NAPEPLD phospholipase D 2.173229 0.02614538 SBDS Shwachman-Bodian-Diamond syndrome 2.17005 0.01655807 SEC62 SEC62 homolog (S. cerevisiae) 2.169831 0.04532519 HNRNPA3 heterogeneous nuclear ribonucleoprotein A3 2.168628 0.02389785 WDR67 WD repeat domain 67 2.167434 0.00446287 ATF7 activating transcription factor 7 2.166594 0.03631358 PRP4 pre-mRNA processing factor 4 PRPF4B homolog B (yeast) 2.165609 0.03223181 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P value SEC31A SEC31 homolog A (S. cerevisiae) 2.1652 0.02487707 SNX14 sorting nexin 14 2.165102 0.00817069 TPRXL tetra-peptide repeat homeobox-like 2.16455 0.03297741 5-methyltetrahydrofolate -homocysteine MTR methyltransferase reductase 2.163555 0.00590251 small nuclear ribonucleoprotein 27kDa SNR P27 (U4/U6.U5) 2.162445 0.00100547 DCTN6 dynactin 6 2.162306 0.01377062 bromodomain and WD repeat domain BRWD1 containing 1 2.160193 0.03029809 ADP-ribosylation factor GTPase activating ARFGAP1 protein 1 2.158847 0.00933169 OSTC oligosaccharyltransferase complex subunit 2.158351 0.04226552 uveal autoantigen with coiled-coil domains UACA and ankyrin repeats 2.154989 0.04375681 SEC24B SEC24 family, member B (S. cerevisiae) 2.151645 0.01992121 MYOIB myosin IB 2.15138 0.0258798 RBM28 RNA binding motif protein 28 2.14976 0.01120596 ubiquitin-conjugating enzyme E2E 1 UBE2E1 (UBC4/5 homolog, yeast) 2.148221 0.02655605 DUS4L dihydroundine synthase 4-like (S. cerevisiae) 2.144957 0.0021074 ubiquitin protein ligase E3 component n- UBR3 recognin 3 (putative) 2.144184 0.04480702 C or 95 chromosome 1 open reading frame 95 2.144175 0.02655454 NIF3 NGG1 interacting factor 3-like 1 (S. NIF3L1 pombe) 2.141869 0.03166882 ZSWIM1 zinc finger, SWIM-type containing 1 2.139669 0.02872817 Proteasome (prosome, macropain) 26S PSMD6 subunit, non-ATPase, 6 2.138274 0.03380946 prostate transmembrane protein, androgen PMEPA1 induced 1 2.137851 0.04356498 UBXN4 UBX domain protein 4 2.134574 0.03656636 RNA (guanine-9-) methyltransferase domain RG9MTD1 containing 1 2.132406 0.00135426 WDFY3 WD repeat and FYVE domain containing 3 2.132311 0.02184892 eukaryotic translation initiation factor 2-alpha EIF2AK1 kinase 1 2.131712 0.04290871 PELO pelota homolog (Drosophila) 2.130176 0.03684364 UNC50 unc-50 homolog (C. elegans) 2.129257 0.03952495 RHBDD2 rhomboid domain containing 2 2.12889 0.0188589 Adaptor protein, phosphotyrosine interaction, APPL1 PH domain and leucine zipper containing 1 2.127615 0.0201 1287 CSNK1G3 casein kinase 1, gamma 3 2.125913 0.04493096 ZNF514 zinc finger protein 514 2.123776 0.0050203 tyrosine 3-monooxygenase/tryptophan 5- monooxygenase activation protein, theta YWHAQ polypeptide 2.122941 0.02980982 ESF1, nucleolar pre-rRNA processing ESF1 protein, homolog (S. cerevisiae) 2.1 19551 0.0214415 ANXA5 annexin A5 2.1 17766 0.02732088 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Chan value AFTPH aftiphilin 2.1 17749 0.03049236 RFC1 replication factor C (activator 1) 1, 145kDa 2.1 16992 0.00583182 La ribonucleoprotein domain family, member LARP1 1 2.1 16245 0.04277522 thioredoxin domain containing 12 TXNDC12 (endoplasmic reticulum) 2.113176 0.01256333 protein phosphatase 2, regulatory subunit B', PPP2R5A alpha 2.11295 0.00397717 human immunodeficiency virus type I HIVEP2 enhancer binding protein 2 2.1 12354 0.03843608 POGZ pogo transposable element with ZNF domain 2.1 11922 0.03641985 UBA6 ubiquitin-like modifier activating enzyme 6 2.1 11562 0.00068623 MCHR2 melanin-concentrating hormone receptor 2 2.111065 0.02992327 trimethylguanosine synthase homolog (S. TGS1 cerevisiae) 2.1 10798 0.00993222 small nuclear ribonucleoprotein polypeptide SNRPA A 2.1 10065 0.04567239 SLC44A4 solute carrier family 44, member 4 2.109894 0.00186453 ZNF354A zinc finger protein 354A 2.109637 0.03065182 KLHL12 kelch-like 12 (Drosophila) 2.109343 0.00422031 B3GALNT2 beta-1 ,3-N-acetylgalactosaminyltransferase 2 2.107978 0.02873171 KIAA0182 KIAA0182 2.105678 0.00027903 dual serine/threonine and tyrosine protein DSTYK kinase 2.102727 0.02592546 FUS interacting protein (serine/arginine-rich) FUSIP1 1 2.102131 0.02330608 FAM13B family with sequence similarity 13, member B 2.10149 0.01852387 deoxynucleotidyltransferase, terminal, DNTTIP2 interacting protein 2 2.099591 0.00861354 TJP2 tight junction protein 2 (zona occludens 2) 2.09871 1 0.01329586 RAP1GDS1 RAP1, GTP-GDP dissociation stimulator 1 2.096922 0.01049954 transmembrane 9 superfamily protein member TM9SF4 4 2.095538 0.01990121 ZNF642 zinc finger protein 642 2.094272 0.03423278 KDM3B lysine (K)-specific demethylase 3B 2.094253 0.01362526 TUBA4B tubulin, alpha 4b (pseudogene) 2.093234 0.04030352 CLCNKB chloride channel Kb 2.091022 0.00559579 SMAP1 small ArfGAP 1 2.089852 0.00484321 discoidin, CUB and LCCL domain containing DCBLD2 2 2.089302 0.04770933 FBXOll F-box protein 11 2.088507 0.0217985 RBM15 RNA binding motif protein 15 2.087109 0.02343943 F 1 fibronectin 1 2.086645 0.02269285 regulation of nuclear pre-mRNA domain RPRD2 containing 2 2.084123 0.04290636 OSBPL7 oxysterol binding protein-like 7 2.083875 0.04973404 PDS5, regulator of cohesion maintenance, PDS5A homolog A (S. cerevisiae) 2.082805 8.27E-05 RPL19 ribosomal protein L 9 2.082173 0.00150615 E2F3 E2F transcription factor 3 2.079912 0.02457361 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value leukocyte immunoglobulin-like receptor, LILRA6 subfamily A (with TM domain), member 6 2.078825 0.02342479 I TS3 integrator complex subunit 3 2.076955 0.03874923 YIPF5 Yipl domain family, member 5 2.076073 0.03670269 HIST1H2BK histone cluster 1, H2bk 2.075114 0.0466658 eukaryotic translation elongation factor 1 beta EEF1B2 2 2.074873 0.00215122 ZNF800 zinc finger protein 800 2.074305 0.00349819 ZMYM2 zinc finger, MYM-type 2 2.074188 0.03424201 C10orfH8 chromosome 10 open reading frame 118 2.073993 0.044251 12 family with sequence similarity 105, member FAM105B B 2.072397 0.02274536 KDM3A lysine (K)-specific demethylase 3A 2.071821 0.01219305 proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic PRG2 protein) 2.071409 0.00277223 DCDC2 doublecortin domain containing 2 2.070271 0.02643862 TET2 tet oncogene family member 2 2.068443 0.02470754 mitogen-activated protein kinase kinase MAP4 4 kinase kinase 4 2.068156 0.00788839 TFB2M transcription factor B2, mitochondrial 2.068018 0.035821 13 protein phosphatase 1, regulatory (inhibitor) PPP1R15B subunit 15B 2.067971 0.00766167 MESDC1 mesoderm development candidate 1 2.066987 0.01694928 GJA9 gap junction protein, alpha 9, 59kDa 2.065205 0.01443866 HTATSF1 HIV- 1 Tat specific factor 1 2.065056 0.0459091 1 family with sequence similarity 91, member FAM91A1 A l 2.064779 0.04939123 TAGAP T-cell activation GTPase activating protein 2.064374 0.04064409 GPATCH1 G patch domain containing 1 2.064054 0.00269694 LRRC40 leucine rich repeat containing 40 2.063667 0.0216401 TTC1 tetratricopeptide repeat domain 1 2.063528 0.04752468 transient receptor potential cation channel, TRPM7 subfamily M, member 7 2.062142 0.04289137 KLK12 kallikrein-related peptidase 12 2.061609 0.04666684 SEC 13 SEC 13 homolog (S. cerevisiae) 2.05941 1 0.00145595 origin recognition complex, subunit 2-like ORC2L (yeast) 2.058017 0.0413684 NAV2 neuron navigator 2 2.05691 0.03319842 C4orf7 chromosome 4 open reading frame 7 2.055779 0.04168687 ARP3 actin-related protein 3 homolog B ACTR3B (yeast) 2.053373 0.03786555 BAIAP2 BAll -associated protein 2 2.053273 0.04228088 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 2.052557 0.02683413 ubiquitin-conjugating enzyme E2E 2 UBE2E2 (UBC4/5 homolog, yeast) 2.050191 0.00816482 EIF4E eukaryotic translation initiation factor 4E 2.049544 0.0267098 dolichyl-diphosphooligosaccharide-protein DDOST glycosyltransferase 2.049205 0.03395848 BAX BCL2-associated X protein 2.048317 0.039567 IB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value intraflagellar transport 140 homolog IFT140 (Chlamydomonas) 2.04779 0.03465379 ZNF440 zinc finger protein 440 2.045831 0.01031447 TMEM39B transmembrane protein 39B 2.045654 0.00057521 HEATR1 HEAT repeat containing 1 2.045248 0.04601 141 M-phase phosphoprotein 10 (U3 small MPHOSPH10 nucleolar ribonucleoprotein) 2.045137 0.0353561 NGLY1 N-glycanase 1 2.04495 0.02465891 TPK1 thiamin pyrophosphokinase 1 2.044392 0.01332447 NUMBL numb homolog (Drosophila)-like 2.044282 0.02042735 TNF receptor-associated factor 3 interacting TRAF3IP1 protein 1 2.041668 0.01902153 Y0 7B myosin VIIB 2.040729 0.03517199 ZNF280D zinc finger protein 280D 2.040638 0.01287239 GON4L gon-4-like (C. elegans) 2.039724 0.00904551 CARD6 caspase recruitment domain family, member 6 2.039599 0.03505956 PMPCB peptidase (mitochondrial processing) beta 2.037316 0.0072201 RAI14 retinoic acid induced 14 2.037265 0.01396032 MRPS2 Mitochondrial ribosomal protein S2 2.036969 0.01324621 PTGES prostaglandin E synthase 2.036575 0.03336 AHI1 Abelson helper integration site 1 2.035579 0.04434107 PNA4 karyopherin alpha 4 (importin alpha 3) 2.033804 0.0449059 6-phosphofructo-2-kinase/fructose-2,6- PFKFB2 biphosphatase 2 2.033696 0.01710018 MRPL9 mitochondrial ribosomal protein L9 2.03358 0.0281763 CD99 CD99 molecule 2.032985 0.02604604 SV2A synaptic vesicle glycoprotein 2A 2.032477 0.00939645 TNPOl transportin 1 2.032411 0.03457859 CLCN3 chloride channel 3 2.032305 0.03797608 SLC25A36 solute carrier family 25, member 36 2.031 104 0.01642812 FBXO30 F-box protein 30 2.030227 0.03710819 VARS valyl-fRNA synthetase 2.029225 0.01223473 epidermal growth factor receptor pathway EPS8 substrate 8 2.029185 0.01334663 succinate-CoA ligase, ADP-forming, beta SUCLA2 subunit 2.028111 0.02841861 LOC440258 similar to p40 2.027771 0.02833365 MOCO sulphurase C-terminal domain MOSC2 containing 2 2.027181 0.00651 172 PPP4R2 Protein phosphatase 4, regulatory subunit 2 2.027077 0.02103272 CCNH cyclin H 2.023407 0.01901314 LARS Leucyl-tRNA synthetase 2.023019 0.04063478 ZNF680 zinc finger protein 680 2.020695 0.04882328 CCNT2 cyclin T2 2.020354 0.02162493 FBXL5 F-box and leucine-rich repeat protein 5 2.020009 0.02326966 family with sequence similarity 175, member FAM175A A 2.019364 0.02563397 ANKRD28 ankyrin repeat domain 28 2.018849 0.01234883 Amyotrophic lateral sclerosis 2 (juvenile) ALS2CR12 chromosome region, candidate 1 2.018779 0.0246608 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value MAGEA10 melanoma antigen family A, 1 2.017044 0.00170272 CXorf48 chromosome X open reading frame 48 2.015612 0.00266866 mitochondrial translational release factor 1- MTRF1L like 2.015598 0.02725181 C18orfl0 chromosome 18 open reading frame 10 2.015562 0.03614906 ZIC4 Zic family member 4 2.014997 0.01917248 KLHL8 kelch-like 8 (Drosophila) 2.014654 0.01102863 MAP4 microtubule-associated protein 4 2.014438 0.02834198 C2orf34 chromosome 2 open reading frame 34 2.013589 0.01841428 ACTR2 ARP2 actin-related protein 2 homolog (yeast) 2.013524 0.01953361 TINP1 TGF beta-inducible nuclear protein 1 2.012733 0.01185654 RRM2 ribonucleotide reductase M2 2.012222 0.02429985 ZNF808 zinc finger protein 808 2.011438 0.01431641 eukaryotic translation initiation factor 4E EIF4E3 family member 3 2.01088 0.00176835 solute carrier family 24 (sodium/potassium/ calcium exchanger), SLC24A2 member 2 2.0101 15 0.00773363 solute carrier family 30 (zinc transporter), SLC30A9 member 9 2.0091 16 0.04176149 TC transcription factor 15 (basic helix-loop-helix) 2.008698 0.01765963 NBEAL1 neurobeachin-like 1 2.007726 0.0082173 DECR1 2,4-dienoyl CoA reductase 1, mitochondrial 2.006511 0.02598747 YIPF7 Yipl domain family, member 7 2.005932 0.03323522 guanine nucleotide binding protein-like 3 GNL3 (nucleolar) 2.005014 0.01735622 OMA1 homolog, zinc metallopeptidase (S. OMA1 cerevisiae) 2.004871 0.02245231 PPHLN1 periphilin 1 2.004551 0.0049265 CLK1 CDC-like kinase 1 2.004524 0.04900386 capping protein (actin filament) muscle Z- CAPZA1 line, alpha 1 2.003944 0.00987919 CANX calnexin 2.003539 0.03158557 SPTBN1 spectrin, beta, non-erythrocytic 1 2.003526 0.01072906 RIP 2 receptor-interacting serine-threonine kinase 2 2.003357 0.03042595 DIAPH1 diaphanous homolog 1 (Drosophila) 2.00281 0.01282001 ENSA endosulfme alpha 1.99941 1 0.03603591 regulatory factor X, 4 (influences HLA class RFX4 II expression) 1.997391 0.03304527 MAPK9 mitogen-activated protein kinase 9 1.995129 0.01967538 Ras association (RalGDS/AF-6) domain RASSF2 family member 2 1.993259 0.03641806 MFN2 mitofusin 2 1.992952 0.03221295 RCOR3 REST corepressor 3 1.992215 0.02218741 acidic (leucine-rich) nuclear phosphoprotein ANP32C 32 family, member C 1.992162 0.00301849 GBA2 glucosidase, beta (bile acid) 2 1.991158 0.02064247 HOXA1 homeobox A l 1.989685 0.00084825 poly(A) binding protein, cytoplasmic 4 PABPC4 (inducible form) 1.988884 0.041 15414 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value PALB2 partner and localizer of BRCA2 1.988632 8.7529E-05 ADAM metallopeptidase with ADAMTS19 thrombospondin type 1 motif, 9 1.987229 0.04221038 FH fumarate hydratase 1.987209 0.01470817 PAX interacting (with transcription-activation PAXIP1 domain) protein 1 1.987167 0.00945075 C4orf30 Chromosome 4 open reading frame 30 1.986477 0.03376819 MAP IB microtubule-associated protein B 1.986421 0.04501 189 CYTL1 cytokine-like 1 1.986119 0.02339349 family with sequence similarity 6, member FAM36A A 1.984139 0.01021283 EOMES eomesodermin homolog (Xenopus laevis) 1.983701 0.03056956 Asparagine-linked glycosylation 13 homolog ALG13 (S. cerevisiae) 1.983324 0.01607156 SCYL2 SCYl-like 2 (S. cerevisiae) 1.982964 0.02371303 TGFB2 transforming growth factor, beta 2 1.98254 0.00552652 PTPRF protein tyrosine phosphatase, receptor type, F 1.98214 0.01266958 sine oculis binding protein homolog SOBP (Drosophila) 1.981332 0.0455914 NRBP1 nuclear receptor binding protein 1 1.980841 0.02904591 VEGFC vascular endothelial growth factor C 1.980744 0.03038233 SLBP stem-loop binding protein 1.980568 0.02420595 ZNF703 zinc finger protein 703 1.980407 0.03514242 MAEL maelstrom homolog (Drosophila) 1.979551 0.01975137 zinc finger (CCCH type), RNA-binding motif ZRSR2 and serine/arginine rich 2 1.979446 0.01662268 STAG3L1 stromal antigen -like 1 1.978732 0.03091 25 bromodomain adjacent to zinc finger domain, BAZ1A 1A 1.978716 0.04410899 JAZF1 JAZF zinc finger 1 1.9781 19 0.01784466 ITGB1BP1 integrin beta 1 binding protein 1 1.976987 0.01098471 cold shock domain containing El , RNA- CSDE1 binding 1.976748 0.00578696 ZNF146 zinc finger protein 146 1.976382 0.0063506 required for meiotic nuclear division 1 PvMNDl homolog (S. cerevisiae) 1.976076 0.01276677 Cllorf24 chromosome 1 open reading frame 24 1.976002 0.03708733 interleukin 6 signal transducer (gpl30, IL6ST oncostatin M receptor) 1.974678 0.03531945 HMGB2 high-mobility group box 2 1.972844 0.03882638 WNK1 WNK lysine deficient protein kinase 1 1.972532 0.03135278 SYNE1 spectrin repeat containing, nuclear envelope 1 1.972468 0.02203298 ENOX2 ecto-NOX disulfide-thiol exchanger 2 1.972447 0.00185752 TRIO triple functional domain (PTPRF interacting) 1.971861 0.04525982 SNX25 sorting nexin 25 1.97084 0.02835255 PDCD6IP programmed cell death 6 interacting protein 1.970203 0.00643999 polycystic kidney and hepatic disease 1 P HD 1 (autosomal recessive) 1.96957 0.04031886 RPAP2 RNA polymerase II associated protein 2 1.968633 0.04430806 FOXP4 forkhead box P4 1.96737 0.02497707 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CCDC106 coiled-coil domain containing 106 0.03760185 KIAA1244 KIAA1244 0.02415564 heterogeneous nuclear ribonucleoprotein L- HNRPLL like 0.02133848 SMN1 survival of motor neuron 1, telomeric 0.01301356 solute carrier family 22 (organic SLC22A5 cation/carnitine transporter), member 5 1.964157 0.01562213 NADH dehydrogenase (ubiquinone) 1 alpha NDUFA5 subcomplex, 5, 13kDa 0.0163378 ZFYVE16 zinc finger, FYVE domain containing 16 0.02898199 SCAMPI secretory carrier membrane protein 1 0.01389306 LSM3 homolog, U6 small nuclear RNA LSM3 associated (S. cerevisiae) 0.040095 ZNF383 zinc finger protein 383 0.02949167 HDAC1 histone deacetylase 1 0.0333261 1 synaptotagmin binding, cytoplasmic RNA SYNCRIP interacting protein 0.0125552 GLCCI1 glucocorticoid induced transcript 1 0.02892498 NARG1L NMDA receptor regulated 1-like 0.03712153 ACAT2 acetyl-CoA acetyltransferase 2 0.02631314 HEXB hexosaminidase B (beta polypeptide) 0.02870889 ZMAT3 zinc finger, matrin type 3 0.02830097 SRPKl SFRS protein kinase 1 0.040619 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated MLLT4 to, 4 0.02928524 EPS8L1 EPS8-like 1 0.02393049 phosphatidylinositol-4-phosphate 5-kinase, PIP5K1A type I, alpha 0.02814202 RNF2 ring finger protein 2 0.00229371 MYT1L Myelin transcription factor 1-like 0.0270455 HSD17B13 N/A 0.0107758 FOXN2 forkhead box N2 0.00671655 ARL13B ADP-ribosylation factor-like 13B 0.02765269 OTOA otoancorin 0.03858649 DOCK 10 dedicator of cytokinesis 10 0.04532886 transmembrane anterior posterior TAPT1 transformation 1 0.03685464 HERC2 hect domain and RLD 2 0.01772168 ZNF585A zinc finger protein 585A 0.01764023 ras-related C3 botulinum toxin substrate 3 RAC3 (rho family, small GTP binding protein Rac3) 0.01804715 PEX1 peroxisomal biogenesis factor 1 0.04410996 UBP1 upstream binding protein 1 (LBP-la) 0.02987965 CRTAP cartilage associated protein 0.02923402 SNX5 sorting nexin 5 0.00305077 ashl (absent, small, or homeotic)-like ASH1L (Drosophila) 0.00682926 low density lipoprotein receptor-related LRP10 protein 10 0.03200017 1/ 69437516.1 Supplemental Table 1. Gene Transcripts pre ated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value family with sequence similarity 168, member FAM168B B 1.94061 0.01272885 CHN1 chimerin (chimaerin) 1 1.940576 0.04939486 Clorfl07 chromosome 1 open reading frame 107 1.940243 0.00831193 STMN3 stathmin-like 3 1.940169 0.00605162 GDI2 GDP dissociation inhibitor 2 1.939501 0.0168794 NCOR2 nuclear receptor co-repressor 2 1.938642 0.01865703 solute carrier family 13 (sodium/sulfate SLC13A1 symporters), member 1 1.938483 0.03936365 SPATA5 Spermatogenesis associated 5 1.938449 0.01321604 APEX nuclease (multifunctional DNA repair APEX1 enzyme) 1 1.937633 0.01208949 GSG1 germ cell associated 1 1.937607 0.00648467 CDK8 cyclin-dependent kinase 8 1.937355 0.03136558 ATP-binding cassette, sub-family E (OABP), ABCE1 member 1 1.937131 0.02691982 NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931 KIF14 kinesin family member 1 1.936247 0.0032016 EIF2C3 eukaryotic translation initiation factor 2C, 3 1.935179 0.01426257 METTL8 methyltransferase like 8 1.935148 0.021 12268 GOLGA6 Golgi autoantigen, golgin subfamily a, 6 1.933403 0.04515888 ARHGAP10 Rho GTPase activating protein 10 1.93239 0.04924193 FANCL Fanconi anemia, complementation group L 1.931456 0.02324647 SH3 domain containing, Ysc84-like 1 (S. SH3YL1 cerevisiae) 1.930488 0.00369118 CCND1 Cyclin Dl 1.930024 0.02353764 TMEM43 transmembrane protein 43 1.9291 0.03823184 ST 4 serine/threonine kinase 4 1.928017 0.04964894 BCAP29 B-cell receptor-associated protein 29 1.927448 0.02335138 protein phosphatase 3, regulatory subunit B, PPP3R1 alpha 1.927241 0.00379102 ClOorfSl chromosome 10 open reading frame 8 1 1.926848 0.02650434 GUF1 GUF1 GTPase homolog (S. cerevisiae) 1.925977 0.00983607 FAM71B family with sequence similarity 71, member B 1.925723 0.03504079 FKSG2 apoptosis inhibitor pseudogene 1.925185 0.02233347 KIAA1715 KIAA1715 1.924517 0.00309567 HDLBP high density lipoprotein binding protein 1.923995 0.0317557 MARS2 methionyl-tRNA synthetase 2, mitochondrial 1.922729 0.0316077 CARKD carbohydrate kinase domain containing 1.922615 0.02370834 RIF1 RAP1 interacting factor homolog (yeast) 1.921728 0.00139196 ITSN1 intersectin 1 (SH3 domain protein) 1.920858 0.04228789 BLZF1 basic leucine zipper nuclear factor 1 1.920386 0.01207716 AKAP13 A kinase (PRKA) anchor protein 13 1.919293 0.0199231 MRPL30 Mitochondrial ribosomal protein L30 1.918716 0.03846072 PFKP phosphofructokinase, platelet 1.915717 0.03636159 TRIM46 tripartite motif-containing 46 1.915667 0.04531322 DLX6 Distal-less homeobox 6 1.915346 0.0157222 Clorf2 Chromosome 1 open reading frame 2 1.913413 0.03292338 CCDC14 coiled-coil domain containing 14 1.912883 0.03675871 C6orfl30 chromosome 6 open reading frame 130 1.912328 0.03702703 1/ 694375 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fo d Ttest P Change value TRIM7 tripartite motif-containing 7 1.911771 0.04613831 Ctr9, Pafl/RNA polymerase II complex CTR9 component, homolog (S. cerevisiae) 1.91 141 1 0.00146435 mesoderm induction early response , family MIER3 member 3 1.91 1318 0.03539947 CDCA7 cell division cycle associated 7 1.909849 0.02148121 general transcription factor IIIC, polypeptide GTF3C3 3, 102kDa 1.909257 0.02969776 SH3 domain binding glutamic acid-rich SH3BGRL2 protein like 2 1.908088 0.04631696 MARK3 MAP/microtubule affinity-regulating kinase 3 1.907991 0.02768508 retinal pigment epithelium-specific protein RPE65 65kDa 1.907053 0.03622687 TCDD-inducible poly(ADP-ribose) TIPARP polymerase 1.905094 0.00574133 ZFC3H1 zinc finger, C3H I-type containing 1.900462 0.02823067 EPB41L2 erythrocyte membrane protein band 4.1-like 2 1.900297 0.01730491 OAZ1 ornithine decarboxylase antizyme 1 1.900225 0.02095961 C6orf72 chromosome 6 open reading frame 72 1.897897 0.02078785 coatomer protein complex, subunit beta 2 COPB2 (beta prime) 1.897638 0.00131933 NUB1 negative regulator of ubiquitin-like proteins 1 1.897502 0.02103466 fatty acid desaturase domain family, member FADS 6 6 1.894571 0.03555164 RINT1 RAD50 interactor 1 1.893722 0.04722573 MGC72080 MGC72080 pseudogene 1.892463 0.03778642 signal transducer and activator of STAT6 transcription 6, interleukin-4 induced 1.892197 0.02746931 solute carrier family 30 (zinc transporter), SLC30A6 member 6 1.891436 0.04633887 UBA5 ubiquitin-like modifier activating enzyme 5 1.891374 0.00330857 ATPase, Na+/K+ transporting, beta 3 ATP1B3 polypeptide 1.889678 0.03406585 SCFD2 seel family domain containing 2 1.888964 0.04069324 STX7 syntaxin 7 1.888885 0.02528416 NCOA7 nuclear receptor coactivator 7 1.888606 0.03681894 ATP-binding cassette, sub-family B ABCB10 (MDR/TAP), member 10 1.888537 0.03715891 NBR1 neighbor ofBRCAl gene 1 1.888532 0.01926365 C16orf89 chromosome 16 open reading frame 89 1.887752 0.03611261 COPA coatomer protein complex, subunit alpha 1.887729 0.00523307 C5orf30 chromosome 5 open reading frame 30 1.887009 0.04109688 BRD2 bromodomain containing 2 1.886865 0.02782694 CSF1R colony stimulating factor 1 receptor 1.886363 0.02272235 VPS13B vacuolar protein sorting 13 homolog B (yeast) 1.883804 0.02306275 EVI5 ecotropic viral integration site 5 1.883555 0.02040397 SLC35A4 solute carrier family 35, member A4 1.882568 0.0078888 PUM1 pumilio homolog 1 (Drosophila) 1.882087 0.0152859 CCDC50 coiled-coil domain containing 50 1.88064 0.01476253 CNOT4 CCR4-NOT transcription complex, subunit 4 1.880325 0.03303252 )B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value DEAH (Asp-Glu-Ala-His) box polypeptide DHX16 16 1.878271 0.03067186 proteasome (prosome, macropain) subunit, PSMB1 beta type, 1 1.877973 0.0332617 R ASEH1 ribonuclease HI 1.877097 0.04098147 SCAPER S-phase cyclin A-associated protein in the ER 1.877076 0.03100614 CD47 CD47 molecule 1.87569 0.01888597 small nucleolar RNA host gene 3 (non-protein SNHG3 coding) 1.874207 0.03386067 cytochrome c oxidase subunit Vila COX7A2L polypeptide 2 like 1.873646 0.01067705 OCLM oculomedin 1.87256 0.01814809 TAPBP TAP binding protein (tapasin) 1.872215 0.00473798 DnaJ (Hsp40) homolog, subfamily A, DNAJA2 member 2 1.871391 0.04124373 integrin, alpha 3 (antigen CD49C, alpha 3 ITGA3 subunit of VLA-3 receptor) 1.870354 0.01607103 ZFP62 Zinc finger protein 62 homolog (mouse) 1.870152 0.0367302 centrosome and spindle pole associated CSPP1 protein 1 1.870004 0.01855885 ATP synthase, H+ transporting, mitochondrial ATP5I F0 complex, subunit E 1.869679 0.04573862 RUFY3 RUN and FYVE domain containing 3 1.86885 0.02251787 CAPN2 calpain 2, (m/II) large subunit 1.868506 0.02067163 MAL2 mal, T-cell differentiation protein 2 1.868321 0.03505472 NCK1 NCK adaptor protein 1 1.868271 0.04033407 FBXL6 F-box and leucine-rich repeat protein 6 1.86584 0.00455271 NBPF3 neuroblastoma breakpoint family, member 3 1.865622 0.01 157426 YY1 YY1 transcription factor 1.865234 0.03212851 glutamine~fructose-6-phosphate transaminase GFPT1 1 1.865212 0.0396156 telomeric repeat binding factor (NIMA- TERF1 interacting) 1 1.863569 0.01246509 RYR2 ryanodine receptor 2 (cardiac) 1.862881 0.00676912 SERTAD2 SERTA domain containing 2 1.862785 0.04590001 DNA fragmentation factor, 45kDa, alpha DFFA polypeptide 1.862478 0.00013042 CS D1 CUB and Sushi multiple domains 1 1.862332 0.04201276 vacuolar protein sorting 54 homolog (S. VPS54 cerevisiae) 1.861531 0.02581 85 BHLHE40 basic helix-loop-helix family, member e40 1.861054 0.03922092 TXLNA taxilin alpha 1.860106 0.01027444 transcription termination factor, RNA TTF2 polymerase II 1.860101 0.01263657 ZNF675 zinc finger protein 675 1.859548 0.02027401 TPD52L1 tumor protein D52-like 1 1.85881 0.02469977 WDR1 WD repeat domain 1 1.858527 0.02723528 ADAM 17 ADAM metallopeptidase domain 1 1.85588 0.03368281 ZMYM1 zinc finger, MYM-type 1 1.855192 0.02837831 SRP14 signal recognition particle 14kDa 1.854744 0.04366461 DB1/ 69 37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value (homologous Alu RNA binding protein) Cell division cycle 2-like 5 (cholinesterase- CDC2L5 related cell division controller) 1.851878 0.03689202 TCTEX1D2 Tcte l domain containing 2 1.851061 0.02861069 mitogen-activated protein kinase associated MAPKAP1 protein 1 1.850653 0.00888942 CAP-GLY domain containing linker protein CLIP4 family, member 4 1.850067 0.02074231 GNPDA1 glucosamine-6-phosphate deaminase 1 1.850039 0.01637317 TUBA1C tubulin, alpha 1c 1.849291 0.00660798 ITIH5 inter-alpha (globulin) inhibitor H5 1.848427 0.03200304 GPX6 Glutathione peroxidase 6 (olfactory) 1.847981 0.00687069 OSBPL8 oxysterol binding protein-like 8 1.847204 0.02216573 USP37 ubiquitin specific peptidase 37 1.846954 0.01682321 RP5- 1000E10.4 N/A 1.846929 0.04792123 CUL9 cullin 9 1.846152 0.00918915 ZKSCAN1 zinc finger with KRAB and SCAN domains 1 1.846012 0.04781497 AGK acylglycerol kinase 1.845718 0.03987334 C5orf41 chromosome 5 open reading frame 4 1 1.844324 0.02521398 RPS8 ribosomal protein S8 1.843008 0.01 108712 DZIP1 DAZ interacting protein 1 1.842491 0.02740508 IRX6 iroquois homeobox 6 1.841361 0.01970989 SFRS4 splicing factor, arginine/serine-rich 4 1.84064 0.04202668 mitogen-activated protein kinase kinase MAP3K2 kinase 2 1.840608 0.02704039 sulfotransferase family, cytosolic, 2B, SULT2B1 member 1 1.840301 0.00982224 ANKRD13B ankyrin repeat domain 13B 1.839917 0.00584462 10-Sep N/A 1.839698 0.03271688 HSPC159 galectin-related protein 1.838673 0.04609221 Transcriptional adaptor 1 (HFI1 homolog, TADA1L yeast)-like 1.837958 0.04364506 CEP97 centrosomal protein 97kDa 1.836937 0.03083775 SRFBP1 serum response factor binding protein 1 1.836767 0.02852658 protein-kinase, interferon-inducible double stranded RNA dependent inhibitor, repressor PRKRIR of (P58 repressor) 1.836748 0.03060855 proteasome (prosome, macropain) 26S PSMC1 subunit, ATPase, 1 1.83611 0.03905445 COL1A1 collagen, type I, alpha 1 1.835332 0.01491401 POLM polymerase (DNA directed), mu 1.834316 0.00459207 JAG1 Jagged 1 (Alagille syndrome) 1.834226 0.04605491 FHOD1 formin homology 2 domain containing 1 1.834128 0.03048125 family with sequence similarity 79, member FAM179B B 1.834068 0.01655335 GYG1 glycogenin 1 1.833606 0.0066626 MANEA mannosidase, endo-alpha 1.833248 0.00915157 transcription factor 3 (E2A immunoglobulin TCF3 enhancer binding factors E12/E47) 1.832816 0.02904369 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CRLF3 cytokine receptor-like factor 3 1.832458 0.00595834 LASP1 LIM and SH3 protein 1 1.83209 0.01310591 ATG5 autophagy related 5 homolog (S. ATG5 cerevisiae) 1.832006 0.02084733 CEP70 centrosomal protein 70kDa 1.829564 0.02190007 CAST calpastatin 1.82713 0.036828 BBX bobby sox homolog (Drosophila) 1.826748 0.04610618 IP09 importin 9 1.82644 0.00165259 TXNDC15 thioredoxin domain containing 15 1.825123 0.04375771 intraflagellar transport 122 homolog IFT122 (Chlamydomonas) 1.825087 0.00170948 YAP1 Yes-associated protein 1 1.824953 0.04116296 MYLK myosin light chain kinase 1.82455 0.00267066 solute carrier family 17 (anion/sugar SLC17A5 transporter), member 5 1.823754 0.01905067 synovial sarcoma, X breakpoint 2 interacting SSX2IP protein 1.823722 0.03458225 MRPL10 Mitochondrial ribosomal protein L10 1.823153 0.03948173 TUB tubby homolog (mouse) 1.821968 0.02603894 HIPK2 Homeodomain interacting protein kinase 2 1.821826 0.04983625 RCVR recoverin 1.820797 0.02437665 KIF3A kinesin family member 3A 1.818053 0.01799915 erythrocyte membrane protein band 4.1 EPB41 (elliptocytosis 1, RH-linked) 1.817829 0.022056 TIA1 cytotoxic granule-associated R A TIA1 binding protein 1.817796 0.02926846 CDC23 Cell division cycle 23 homolog (S. cerevisiae) 1.817618 0.03921417 SAT1 spermidine/spermine Nl-acetyltransferase 1 1.817253 0.01695831 microtubule associated monoxygenase, MICAL2 calponin and LIM domain containing 2 1.817247 0.0077313 C4or£21 chromosome 4 open reading frame 2 1 1.816677 0.04909137 purinergic receptor P2X, ligand-gated ion P2RX1 channel, 1 1.816601 0.00616274 C5orf43 chromosome 5 open reading frame 43 1.81604 0.01543196 proteasome (prosome, macropain) subunit, PSMA7 alpha type, 7 1.814899 0.0228106 C17orf57 chromosome 17 open reading frame 57 1.814854 0.03520185 NADH dehydrogenase (ubiquinone) 1, NDUFC1 subcomplex unknown, 1, 6kDa 1.814744 0.00472754 serine/threonine kinase 25 (STE20 homolog, STK25 yeast) 1.813528 0.02207752 Rho guanine nucleotide exchange factor ARHGEF11 (GEF) 11 1.812046 0.03352064 PK 2 protein kinase N2 1.81078 0.03572897 polymerase (RNA) II (DNA directed) POLR2J4 polypeptide J4, pseudogene 1.810565 0.03929667 blocked early in transport 1 homolog (S. BET1 cerevisiae) 1.810406 0.04306222 RIOK3 RIO kinase 3 (yeast) 1.810224 0.04030526 ATP5B ATP synthase, H+ transporting, mitochondrial 1.809531 0.04418697 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Chan value Fl complex, beta polypeptide ARCN1 archain 1 1.808802 0.02287658 RPL23AP7 ribosomal protein L23a pseudogene 7 1.808578 0.01058161 Rho guanine nucleotide exchange factor ARHGEF10 (GEF) 10 1.807515 0.025471 19 STXBP6 syntaxin binding protein 6 (amisyn) 1.807136 0.04173158 protein tyrosine phosphatase, non-receptor PTPN9 type 9 1.806452 0.03400917 C6orfl50 chromosome 6 open reading frame 150 1.805382 0.00837178 excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B ERCC3 complementing) 1.80534 0.03842784 Clorf9 Chromosome 1 open reading frame 9 1.804845 0.0210386 asp (abnormal spindle) homolog, ASPM microcephaly associated (Drosophila) 1.803894 0.04304251 EDAR ectodysplasin A receptor 1.802901 0.0484354 HECA headcase homolog (Drosophila) 1.80288 0.02267831 roundabout, axon guidance receptor, homolog ROBOl I (Drosophila) 1.802834 0.03733771 KIAA0907 KIAA0907 1.802135 0.01635821 CADM1 cell adhesion molecule 1 1.801595 0.01731324 EIF2C1 eukaryotic translation initiation factor 2C, 1 1.801198 0.02584671 ATXN1 ataxin 1 1.800174 0.04856069 BMX BMX non-receptor tyrosine kinase 1.799917 0.0132007 THUMPD3 THUMP domain containing 3 1.798321 0.02891873 TNNI3K TN I3 interacting kinase 1.796699 0.00422282 DnaJ (Hsp40) homolog, subfamily C, member DNAJC7 7 1.79528 0.04547126 solute carrier family 1 (glutamate/neutral SLC1A4 amino acid transporter), member 4 1.794159 0.0013034 PREPL prolyl endopeptidase-like 1.793794 0.02865172 protein O-linked mannose betal,2-N- POMGNT1 acetylglucosaminyltransferase 1.793763 0.00419277 BBS7 Bardet-Biedl syndrome 7 1.793614 0.0295155 calcium/calmodulin-dependent protein kinase CAMK2A II alpha 1.79334 0.01 140048 DnaJ (Hsp40) homolog, subfamily C, member DNAJC1 1 11 1.792024 0.01033343 solute carrier organic anion transporter SLC03A1 family, member 3A1 1.789337 0.02548138 HNRNPAO heterogeneous nuclear ribonucleoprotein A O 1.789162 0.0369539 NRCAM neuronal cell adhesion molecule 1.788258 0.02131313 family with sequence similarity 128, member FAM128A A 1.787413 0.00608961 STAG3L4 stromal antigen 3-like 4 1.787315 0.04479751 succinate-CoA ligase, GDP-forming, beta SUCLG2 subunit 1.786827 0.00924396 UBXN7 UBX domain protein 7 1.786441 0.0022891 RABGAP1L RAB GTPase activating protein 1-like 1.785973 0.01839424 DBl/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value LMNB1 lamin B l 1.785446 0.02155216 FIG4 homolog, SAC1 lipid phosphatase FIG4 domain containing (S. cerevisiae) 1.784998 0.01721844 LASS2 LAG1 homolog, ceramide synthase 2 1.783932 0.01893847 programmed cell death 4 (neoplastic PDCD4 transformation inhibitor) 1.78353 0.02762895 SAP30 Sin3A-associated protein, 30kDa 1.783367 0.04714102 ZBTB10 zinc finger and BTB domain containing 10 1.783247 0.01564548 CCDC76 coiled-coil domain containing 76 1.78322 0.01357722 NOS2 nitric oxide synthase 2, inducible 1.783161 0.01310977 FBXW7 F-box and WD repeat domain containing 7 1.782983 0.0196405 T IM52 tripartite motif-containing 52 1.782673 0.0424533 SUZ12 suppressor of zeste 12 homolog (Drosophila) 1.781738 0.0427054 SH3GLB2 SH3-domain GRB2-like endophilin B2 1.77951 0.02756375 SCAND3 SCAN domain containing 3 1.779181 0.04344292 MCM3AP antisense RNA (non-protein MCM3APAS coding) 1.777941 0.02758222 WTAP Wilms tumor 1 associated protein 1.777876 0.00868387 ZNF354C zinc finger protein 354C 1.777855 0.0062276 CASP8AP2 caspase 8 associated protein 2 1.77773 0.00912374 CRHR2 corticotropin releasing hormone receptor 2 1.776097 0.00279438 TTRAP TRAF and TNF receptor associated protein 1.775492 0.04327018 AFF3 AF4/FMR2 family, member 3 1.774709 0.04961151 acidic (leucine-rich) nuclear phosphoprotein ANP32A 32 family, member A 1.773795 0.00540646 AKAP8 A kinase (PRKA) anchor protein 8 1.773053 0.00229454 PBRM1 polybromo 1 1.771 167 0.03425846 PM20D1 peptidase M20 domain containing 1 1.770845 0.02670605 IFIH1 interferon induced with helicase C domain 1 1.770252 0.04974546 ICA1 islet cell autoantigen 1, 69kDa 1.770105 0.03019432 AGBL5 ATP/GTP binding protein-like 5 1.770017 0.04332805 NAV3 neuron navigator 3 1.770005 0.04660366 LYG2 lysozyme G-like 2 1.769802 0.01444479 DDR1 discoidin domain receptor tyrosine kinase 1 1.769628 0.02493444 Z F213 zinc finger protein 213 1.76888 0.02160061 ArfGAP with GTPase domain, ankyrin repeat AGAP2 and PH domain 2 1.768822 0.03622317 GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.768741 0.03226337 down-regulator of transcription 1, TBP- DR1 binding (negative cofactor 2) 1.767005 0.02631065 TNXB tenascin XB 1.766861 0.02330234 TAF8 RNA polymerase II, TATA box binding protein (TBP)-associated factor, TAF8 43kDa 1.766752 0.04249763 WDR26 WD repeat domain 26 1.766404 0.04389929 DHCR24 24-dehydrocholesterol reductase 1.76631 1 0.03658698 COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.763676 0.02397798 STXBP4 Syntaxin binding protein 4 1.762673 0.02317395 CTSL1 cathepsin LI 1.762195 0.00671078 ZMYND11 zinc finger, MY D domain containing 11 1.762069 0.04523794 DBl/69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CRISP3 cysteine-rich secretory protein 3 1.761506 0.03613203 FUR F 1 receptor 1.761288 0.02412146 Sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short SEMA4A cytoplasmic domain, (semaphorin) 4A 1.760637 0.00035897 MAM domain containing MDGA1 glycosylphosphatidylinositol anchor 1 1.760367 0.03598768 protein phosphatase 1, regulatory (inhibitor) PPP1R13L subunit 13 like 1.7592 0.04452406 SMYD5 SMYD family member 5 1.758334 0.03952075 SFRS15 splicing factor, arginine/serine-rich 15 1.758154 0.0470158 BAI1 brain-specific angiogenesis inhibitor 1 1.756649 0.00916272 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma ERBB2 derived oncogene homolog (avian) 1.755689 0.02545648 Clorfl68 chromosome 1 open reading frame 168 1.755419 0.03359442 LHFPL4 Lipoma HMGIC fusion partner-like 4 1.754908 0.00212537 RNF5P1 ring finger protein 5 pseudogene 1 1.754173 0.02376122 protein-L-isoaspartate (D-aspartate) 0 - PCMT1 methyltransferase 1.753126 0.01819688 RYK RYK receptor-like tyrosine kinase 1.751 194 0.00185441 adaptor-related protein complex 2, alpha 2 AP2A2 subunit 1.751007 0.01495759 ATP1 B ATPase, class VI, type 1 B 1.750681 0.0249001 1 CNOT8 CCR4-NOT transcription complex, subunit 8 1.750479 0.04298721 eukaryotic translation initiation factor 4 EIF4G1 gamma, 1 1.750254 0.00740522 HOXA13 homeobox A13 1.748129 0.03914432 MRAS muscle RAS oncogene homolog 1.747667 0.0018277 Methylcrotonoyl-Coenzyme A carboxylase 1 MCCC1 (alpha) 1.746294 0.0228626 CD74 molecule, major histocompatibility CD74 complex, class II invariant chain 1.744558 0.0075195 mitogen-activated protein kinase kinase MAP3K7 kinase 7 1.743976 0.02238046 C9orfl40 chromosome 9 open reading frame 140 1.742816 0.03971348 ZNF654 zinc finger protein 654 1.742812 0.01596965 small nuclear ribonucleoprotein polypeptide SNRPC C 1.742362 0.04469681 TSGA10 testis specific, 10 1.741521 0.02049649 PRDM2 PR domain containing 2, with ZNF domain 1.740844 0.04930196 SDAD1 SDA1 domain containing 1 1.740613 0.02810075 ZNF 0 zinc finger protein 510 1.73974 0.00011319 ZFYVE28 zinc finger, FYVE domain containing 28 1.739287 0.01571989 NFE2L3 nuclear factor (erythroid-derived 2)-like 3 1.738235 0.01922635 ZNF384 zinc finger protein 384 1.737747 0.03729418 GNAS GNAS complex locus 1.736578 0.0214594 TUBB4 tubulin, beta 4 1.736534 0.00359016 SFRS12IP1 SFRS12-interacting protein 1 1.736013 0.00899882 PLK2 polo-like kinase 2 (Drosophila) 1.735402 0.03172869 )B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value HSPA4L heat shock 70kDa protein 4-like 1.733956 0.04720531 NKAP NFKB activating protein 1.732831 0.02649561 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL 1-like helicase homolog, DDX1 1 S. cerevisiae) 1.732086 0.00580239 DnaJ (Hsp40) homolog, subfamily B, member DNAJB8 8 1.731683 0.03375359 ZC3H8 zinc finger CCCH-type containing 8 1.731254 0.03446465 DZIP3 DAZ interacting protein 3, zinc finger 1.731 1 1 1 0.02789567 integrin, alpha 2 (CD49B, alpha 2 subunit of ITGA2 VLA-2 receptor) 1.731067 0.03490653 KIAA0528 KIAA0528 1.730924 0.0064972 solute carrier family 2 (facilitated glucose SLC2A1 transporter), member 1 1.730841 0.01057146 LGALS8 lectin, galactoside-binding, soluble, 8 1.73016 0.02373729 serine threonine kinase 39 (STE20/SPS1 STK39 homolog, yeast) 1.729703 0.04202932 TMEM120A transmembrane protein 120A 1.729431 0.04351484 CEP 164 centrosomal protein 164kDa 1.728991 0.01830317 DA S aspartyl-tRNA synthetase 1.728775 0.03291067 phosphoinositide-3-kinase, catalytic, alpha PIK3CA polypeptide 1.728352 0.03384356 family with sequence similarity 8, member FAM8A1 A l 1.727897 0.01676628 LIM and senescent cell antigen-like domains LIMS1 1 1.72779 0.04472927 RPE ribulose-5 -phosphate-3 -epimerase 1.72725 0.04901899 BRMSIL breast cancer metastasis-suppressor 1-like 1.726914 0.03549736 mitochondrial translation optimization 1 MTOl homolog (S. cerevisiae) 1.726686 0.03214024 CROT carnitine O-octanoyltransferase 1.726263 0.02848848 LEF1 Lymphoid enhancer-binding factor 1 1.725065 0.04118395 FIGNL1 fidgetin-like 1 1.724436 0.041 13886 MTMR1 1 myotubularin related protein 11 1.724433 0.00608173 nudix (nucleoside diphosphate linked moiety NUDT12 X)-type motif 2 1.7241 9 0.01468459 PTEN phosphatase and tensin homolog 1.723703 0.03642467 LMBRD1 LMBR1 domain containing 1 1.722225 0.00672219 CCDC138 coiled-coil domain containing 138 1.72192 0.01981292 TSPYL4 TSPY-like 4 1.721806 0.04163103 tankyrase, TRF1 -interacting ankyrin-related TNKS ADP-ribose polymerase 1.721619 0.01032826 heterogeneous nuclear ribonucleoprotein C HNRNPC (C1/C2) 1.721289 0.0451 1126 PLA2G3 phospholipase A2, group III 1.720314 0.01001067 calcium channel, voltage-dependent, L type, CACNA1C alpha 1C subunit 1.720015 0.00384218 TULP3 tubby like protein 3 1.719888 0.00181719 LMBR1 limb region 1 homolog (mouse) 1.719877 0.02991854 TGFBRAP1 transforming growth factor, beta receptor 1.718545 0.00485692 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value associated protein 1 patatin-like phospholipase domain containing PNPLA8 8 1.717105 2.38E-06 C2orf29 chromosome 2 open reading frame 29 1.717065 0.01919981 C18orf21 chromosome 18 open reading frame 2 1 1.716032 0.02987306 SERBP1 SERPINE1 mR A binding protein 1 1.715694 0.01072272 PEX3 peroxisomal biogenesis factor 3 1.714742 0.02148205 echinoderm microtubule associated protein EML4 like 4 1.7145 0.02241195 SORBS2 sorbin and SH3 domain containing 2 1.714498 0.0455495 PTER phosphotriesterase related 1.714416 0.01735673 HDAC2 histone deacetylase 2 1.713956 0.04708192 CENPQ centromere protein Q 1.71339 0.0213132 family with sequence similarity 76, member FAM76A A 1.712509 0.0157301 AIM2 absent in melanoma 2 1.71178 0.00998366 HOOK1 hook homolog 1 (Drosophila) 1.710771 0.0260001 1 ATP-binding cassette, sub-family B ABCB8 (MDR/TAP), member 8 1.710166 0.00861395 CDC40 cell division cycle 40 homolog (S. cerevisiae) 1.709933 0.025953 SLC2A4RG SLC2A4 regulator 1.709081 0.04190288 C7orf38 Chromosome 7 open reading frame 38 1.708807 0.02303838 EPHA3 EPH receptor A3 1.708107 0.02252368 ALS2 Amyotrophic lateral sclerosis 2 (juvenile) 1.707659 0.00694015 FANCC Fanconi anemia, complementation group C 1.707104 0.02702837 CFLAR CASP8 and FADD-like apoptosis regulator 1.706199 0.02074358 MED30 mediator complex subunit 30 1.705178 0.01884414 family with sequence similarity 160, member FAM160A2 A2 1.704982 0.03334977 catenin (cadherin-associated protein), alpha¬ CTNNAL1 like 1 1.704478 0.03948794 KLHL32 kelch-like 32 (Drosophila) 1.704126 0.03211128 G AP1 G kinase anchoring protein 1 1.704021 0.01022421 gamma-aminobutyric acid (GABA) A GABRG2 receptor, gamma 2 1.703807 0.04593652 ALMS1 Alstrom syndrome 1 1.70361 0.04786654 ZNF189 zinc finger protein 1 9 1.702987 0.04710515 NRD1 nardilysin (N-arginine dibasic convertase) 1.702908 0.04096405 TMEM65 transmembrane protein 65 1.702792 0.02059544 Clorf27 chromosome 1 open reading frame 27 1.702394 0.02061163 general transcription factor HE, polypeptide 1, GTF2E1 alpha 56kDa 1.702074 0.04249274 NOLC1 nucleolar and coiled-body phosphoprotein 1 1.70141 0.04459261 PINK1 PTEN induced putative kinase 1 1.701369 0.02986638 AGFG1 ArfGAP with FG repeats 1 1.700814 0.02888252 LHX8 LIM homeobox 8 1.698942 0.00318506 leucine zipper-EF-hand containing LETM1 transmembrane protein 1 1.698753 0.02155205 NIT2 nitrilase family, member 2 1.697659 0.03895012 RNF130 ring finger protein 0 1.697257 0.01 112673 ) 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ZNF286A zinc finger protein 286A 1.69708 0.00059534 RABGAP1 RAB GTPase activating protein 1 1.696465 0.02235212 Src homology 2 domain containing SHD transforming protein D 1.696106 0.033051 13 CD68 CD68 molecule 1.695795 0.00184294 WDR7 WD repeat domain 7 1.694536 0.02634425 JAK1 Janus kinase 1 1.69388 0.01522807 TRIM24 tripartite motif-containing 24 1.69341 1 0.04105101 Transient receptor potential cation channel, TRPV3 subfamily V, member 3 1.693271 0.01071292 protein phosphatase 1, regulatory (inhibitor) PPP1R2 subunit 2 1.693178 0.00191476 staufen, RNA binding protein, homolog 1 STAU1 (Drosophila) 1.693099 0.04965607 PLD3 phospholipase D family, member 3 1.6923 0.04747022 COL5A1 collagen, type V, alpha 1 1.69213 0.04039646 SCD stearoyl-CoA desaturase (delta-9-desaturase) 1.692073 0.02710143 PLXND1 Plexin D l 1.691717 0.02853845 CPNE3 copine III 1.691682 0.00274705 membrane associated guanylate kinase, WW MAG and PDZ domain containing 1 1.691656 0.03053273 MAPK3 mitogen-activated protein kinase 3 1.691005 0.04026195 UVRAG UV radiation resistance associated gene 1.690489 0.03919053 TEX 19 testis expressed 19 1.689462 0.02512695 C8orf33 chromosome 8 open reading frame 33 1.689323 0.0139295 DOPEY2 dopey family member 2 1.68908 0.04094941 DAP death-associated protein 1.688477 0.00441882 WASL Wiskott-Aldrich syndrome-like 1.688132 0.01807076 SAMD4A sterile alpha motif domain containing 4A 1.687902 0.005081 13 DIRC2 disrupted in renal carcinoma 2 1.686764 0.0406976 CDC5L CDC5 cell division cycle 5-like (S. pombe) 1.686596 0.00513394 XRN1 5 -3' exoribonuclease 1 1.685701 0.0437345 SECISBP2 SECIS binding protein 2 1.685434 0.0132207 DnaJ (Hsp40) homolog, subfamily B, member DNAJB6 6 1.68511 0.02203927 COL4A5 collagen, type IV, alpha 5 1.684698 0.0014245 ubiquitin-conjugating enzyme E2H (UBC8 UBE2H homolog, yeast) 1.683991 0.00580532 HMBOX1 homeobox containing 1 1.682653 0.01652019 WDR3 WD repeat domain 3 1.682566 0.01179129 MYOM3 myomesin family, member 3 1.682278 0.01208733 Transcription factor 7-like 1 (T-cell specific, TCF7L1 HMG-box) 1.682274 0.00738236 catenin (cadherin-associated protein), beta 1, CTNNB1 88kDa 1.68156 0.01788189 TYMP thymidine phosphorylase 1.681529 0.04153714 NOSIP nitric oxide synthase interacting protein 1.681421 0.04395 EYA3 eyes absent homolog 3 (Drosophila) 1.681292 0.02095053 SLMAP sarcolemma associated protein 1.681 183 0.044105 GGA2 golgi-associated, gamma adaptin ear 1.679827 0.00751514 B 1/ 69437516.1 Supplemental Tab c 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value containing, ARF binding protein 2 LAMP3 lysosomal-associated membrane protein 3 1.678861 0.02458607 RPL9 ribosomal protein L9 1.678778 0.02683837 TRIT1 tRNA isopenteny transferase 1 1.677877 0.04083159 protein kinase C and casein kinase substrate PACSIN1 in neurons 1 1.676679 0.02027534 SP4 Sp4 transcription factor 1.676382 0.0490481 ribosome binding protein 1 homolog 180kDa RRBP1 (dog) 1.676273 0.03208152 C3orf24 chromosome 3 open reading frame 24 1.676037 0.03229523 TMEM77 Transmembrane protein 77 1.675743 0.01021385 OCIAD1 OCIA domain containing 1 1.675522 0.0099691 tRNA splicing endonuclease 2 homolog (S. TSEN2 cerevisiae) 1.675438 0.02583301 NSL1, MIND kinetochore complex NSL1 component, homolog (S. cerevisiae) 1.675294 0.00175439 ZNF23 zinc finger protein 23 (KOX 16) 1.67496 0.03514622 ZNF302 zinc finger protein 302 1.674077 0.0485076 VTA1 Vps20-associated 1 homolog (S. cerevisiae) 1.673359 0.03794161 SLU7 SLU7 splicing factor homolog (S. cerevisiae) 1.673319 0.04457199 RPL27A ribosomal protein L27a 1.673236 0.01515691 CNK 6 potassium channel, subfamily K, member 16 1.672001 0.02875484 adaptor-related protein complex 2, alpha 1 AP2A1 subunit 1.671987 0.03794131 RGPD2 RANBP2-like and GRIP domain containing 2 1.671712 0.01608914 RPL15 ribosomal protein LI5 1.671399 0.00413895 NAIP NLR family, apoptosis inhibitory protein 1.67134 0.01945006 calcium/calmodulin-dependent protein kinase CAMK2D II delta 1.671216 0.00929113 KIAA1012 KIAA1012 1.671 1 0.0435802 HOOK3 hook homolog 3 (Drosophila) 1.670954 0.03532757 BAI2 brain-specific angiogenesis inhibitor 2 1.670904 0.04007991 BEND7 BEN domain containing 7 1.67085 0.00838852 JUN jun oncogene 1.670629 0.00804181 eukaryotic translation initiation factor 3, EIF3K subunit K 1.669436 0.00274533 WWC3 WWC family member 3 1.667972 0.01632484 ACOX1 Acyl-Coenzyme A oxidase 1, palmitoyl 1.667647 0.00796185 enhancer of polycomb homolog 1 EPC1 (Drosophila) 1.666674 0.01145716 PAIP1 poly(A) binding protein interacting protein 1 1.66649 0.03104414 CDK5RAP2 CDK5 regulatory subunit associated protein 2 1.665978 0.02623349 LPCAT2 lysophosphatidylcholine acyltransferase 2 1.665875 0.03018121 CYB5R4 cytochrome b5 reductase 4 1.665456 0.00509119 PKP2 plakophilin 2 1.665271 0.0236316 ADAMTSL4 ADAMTS-like 4 1.663953 0.03234697 CNOT6 CCR4-NOT transcription complex, subunit 6 1.663682 0.01038354 REV1 REV1 homolog (S. cerevisiae) 1.663518 0.03153223 chaperonin containing TCP1, subunit 3 CCT3 (gamma) 1.663267 0.04685597 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value TBC1D17 TBC1 domain family, member 17 1.66246 0.02023361 LRRC1 Leucine rich repeat containing 1 1.66149 0.01283386 OSBPL6 oxysterol binding protein-like 6 1.661319 0.02184632 CLOCK clock homolog (mouse) 1.660451 0.0374842 recombination activating gene 1 activating RAG1AP1 protein 1 1.660269 0.04756292 PHF15 PHD finger protein 15 1.660195 0.00139822 GORAB golgin, RAB6-interacting 1.660106 0.00607479 hCG 1817306 N/A 1.659972 0.03901822 ERGIC2 ERGIC and golgi 2 1.659425 0.0356255 MKL2 MKL/myocardin-like 2 1.659162 0.00390191 ING2 inhibitor of growth family, member 2 1.657729 0.02121174 CCDC144A coiled-coil domain containing 144A 1.657432 0.00173654 DNHD1 dynein heavy chain domain 1 1.657184 0.01566451 WDR91 WD repeat domain 9 1.656314 0.0315293 CYB561D1 cytochrome b-561 domain containing 1 1.656224 0.01791395 PRDM15 PR domain containing 15 1.655236 0.01 158217 inositol 1,4, -triphosphate receptor interacting ITPRIP protein 1.655234 0.03688571 GAGE1 G antigen 1 1.655031 0.00514216 ANKRD26 ankyrin repeat domain 26 1.654533 0.02552525 ZNF142 zinc finger protein 142 1.654022 0.000781 12 RNF43 Ring finger protein 43 1.65396 0.02379895 DR75 WD repeat domain 75 1.653748 0.0495029 POLK polymerase (DNA directed) kappa 1.653549 0.01193697 HIST1H4L histone cluster 1, H41 1.652972 0.04865703 intraflagellar transport 1 homolog IFT81 (Chlamydomonas) 1.652245 0.0468978 proteasome (prosome, macropain) assembly PSMG2 chaperone 2 1.652182 0.01 16722 C19orfl5 Chromosome 19 open reading frame 1 1.652015 0.0338281 calcium channel, voltage-dependent, gamma CACNG1 subunit 1 1.650647 0.04021915 WWC2 WW and C2 domain containing 2 1.648889 0.04777825 DCP2 decapping enzyme homolog (S. DCP2 cerevisiae) 1.648793 0.0231 128 KRT12 keratin 12 1.64871 1 0.02722292 AN03 anoctamin 3 1.647576 0.02231733 TOR1AIP2 torsin A interacting protein 2 1.647022 0.03031937 DENR density-regulated protein 1.64684 0.00919117 cytochrome P450, family 1, subfamily B, CYP1B1 polypeptide 1 1.646677 0.00867029 RNF214 ring finger protein 214 1.645844 0.01485931 RPL12 ribosomal protein L12 1.645702 0.03148393 SHPRH SNF2 histone linker PHD RING helicase 1.645516 0.03755224 GSK3B glycogen synthase kinase 3 beta 1.644466 0.04817556 Small inducible cytokine subfamily E, SCYE1 member 1 (endothelial monocyte-activating) 1.64437 0.00803724 neural precursor cell expressed, NEDD9 developmentally down-regulated 9 1.644364 0.04275758 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value LICAM LI cell adhesion molecule 1.644025 0.00530349 STK38 serine/threonine kinase 8 1.642924 0.016321 12 PPCS phosphopantothenoylcysteine synthetase 1.642528 0.0195829 PSAP prosaposin 1.642419 0.03606651 ZCCHC6 zinc finger, CCHC domain containing 6 1.64235 0.02301349 SYT10 Synaptotagmin X 1.642079 0.0298561 DNAH1 Dynein, axonemal, heavy chain 1 1.641795 0.02199322 MAP2K5 mitogen-activated protein kinase kinase 5 1.641555 0.0054391 1 MRPS5 mitochondrial ribosomal protein S5 1.641288 0.02848696 G-protein signaling modulator 3 (AGS3-like, GPSM3 C. elegans) 1.641236 0.04995749 MRPL20 Mitochondrial ribosomal protein L20 1.641024 0.02461408 ELAV (embryonic lethal, abnormal vision, ELAVL1 Drosophila)-like 1 (Hu antigen R) 1.640597 0.03564955 TAGLN transgelin 1.640518 0.04817693 ACTL6A actin-like 6A 1.640505 0.04155384 C20orfll4 chromosome 20 open reading frame 114 1.639829 0.00887036 caspase recruitment domain family, member CARD11 1 1 1.639374 0.01315459 SCML2 sex comb on midleg-like 2 (Drosophila) 1.639341 0.03583245 TNS3 tensin 3 1.639279 0.026171 19 ATXN7L1 Ataxin 7-like 1 1.63894 0.00322217 NPHP3 nephronophthisis 3 (adolescent) 1.638935 0.00341519 NSUN5B NOLl/NOP2/Sun domain family, member 5B 1.638557 0.00035345 AES amino-terminal enhancer of split 1.638478 0.04945512 EDC4 enhancer of mRNA decapping 4 1.638271 0.03325857 v-raf murine sarcoma viral oncogene homolog BRAF Bl 1.638003 0.03531981 solute carrier organic anion transporter SLC02A1 family, member 2A1 1.637127 0.0265858 Src homology 3 domain-containing guanine SGEF nucleotide exchange factor 1.636679 0.0107291 1 phosphatidylinositol glycan anchor PIGK biosynthesis, class K 1.6363 0.00319759 SETBP1 SET binding protein 1 1.63618 0.00590179 GEN1 Gen homolog 1, endonuclease (Drosophila) 1.635816 0.02891478 APOB apolipoprotein B (including Ag(x) antigen) 1.635177 0.03837457 KLB klotho beta 1.634465 0.00022703 integrin, alpha E (antigen CD103, human mucosal lymphocyte antigen 1; alpha ITGAE polypeptide) 1.634074 0.03995079 Biphenyl hydrolase-like (serine hydrolase; BPHL breast epithelial mucin-associated antigen) 1.633697 0.01337344 CXorf58 chromosome X open reading frame 58 1.63358 0.00778154 ACTB actin, beta 1.633494 0.04468234 aldehyde dehydrogenase 3 family, member ALDH3B1 Bl 1.63275 0.00741251 SUFU suppressor of fused homolog (Drosophila) 1.632133 0.01242218 ST8 alpha-N-acetyl-neuraminide alpha-2,8- ST8SIA4 sialyltransferase 4 1.631566 0.03915633 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value protein tyrosine phosphatase, non-receptor PTPN14 type 14 1.63156 0.04046252 GI gypsy retrotransposon integrase 1 1.631327 0.03380499 MTIF2 mitochondrial translational initiation factor 2 1.631234 0.04677842 DNAL4 dynein, axonemal, light chain 4 1.630824 0.00553133 ZBTB40 zinc finger and BTB domain containing 40 1.630804 0.0346299 Cl lorfl Chromosome 11 open reading frame 1 1.630803 0.02442311 KIAA0247 KIAA0247 1.630564 0.03640115 ATP4B ATPase, H+/K+ exchanging, beta polypeptide 1.629612 0.04978088 ADAM metallopeptidase with ADAMTS6 thrombospondin type 1 motif, 6 1.629112 0.01365261 CCDC24 coiled-coil domain containing 24 1.629028 0.03641 167 SPEF2 sperm flagellar 2 1.628671 0.02751741 MMP23A matrix metallopeptidase 23A (pseudogene) 1.628276 0.00795961 GPR124 G protein-coupled receptor 124 1.628088 0.03794903 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX56 56 1.627335 0.03177008 ADP-ribosylation-like factor 6 interacting ARL6IP6 protein 6 1.627215 0.03755756 leucine-rich repeats and WD repeat domain LRWD1 containing 1 1.626571 0.03027413 CXorf22 chromosome X open reading frame 22 1.626407 0.04193664 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 1 (GalNAc- GALNT1 Tl) 1.626164 0.03763074 megalencephalic leukoencephalopathy with MLC1 subcortical cysts 1 1.625926 0.0132559 NCRNA0008 3 non-protein coding R A 83 1.625919 0.00905639 MRPL41 mitochondrial ribosomal protein L41 1.625633 0.0209388 inhibitor of Bruton agammaglobulinemia IBTK tyrosine kinase 1.625579 0.01834248 COL27A1 collagen, type XXVII, alpha 1 1.625164 0.02639891 angiogenic factor with G patch and FHA AGGF1 domains 1 1.624279 0.04569015 LPCAT1 lysophosphatidylcholine acyltransferase 1 1.624191 0.04338435 TMEM30A transmembrane protein 30A 1.62414 0.00774066 Γ Ο 80Β INO80 complex subunit B 1.623832 0.04070508 C6orfl Chromosome 6 open reading frame 1 1.623349 0.04350354 GAD1 glutamate decarboxylase 1 (brain, 67kDa) 1.622848 0.02366237 ITPR3 inositol 1,4,5-triphosphate receptor, type 3 1.62276 0.02131997 RANBP3 RAN binding protein 3 1.622539 0.02211052 TRIM37 tripartite motif-containing 37 1.622298 0.0271814 TTC37 tetratricopeptide repeat domain 3 1.622054 0.02753881 TFRC transferrin receptor (p90, CD71) 1.621364 0.02335426 HMCN1 hemicentin 1 1.6206 0.03558657 NUP153 nucleoporin 153kDa 1.619972 0.02029782 AFAP1 actin filament associated protein 1 1.619608 0.04847107 ZSCAN16 zinc finger and SCAN domain containing 16 1.619254 0.03603056 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value RPS6KL1 ribosomal protein S6 kinase-like 1 1.619011 0.01727224 translocation associated membrane protein 1- TRAM1L1 like 1 1.618507 0.04921298 C14orf45 Chromosome 14 open reading frame 45 1.6181 12 0.00555711 PLCGl phospholipase C, gamma 1 1.617724 0.01886621 BAT2L N/A 1.617581 0.02508675 GAK cyclin G associated kinase 1.616995 0.04650567 euchromatic histone-lysine N- EHMT2 methyltransferase 2 1.616535 0.00569505 DnaJ (Hsp40) homolog, subfamily C, member DNAJC13 13 1.616418 0.01480203 PARP1 poly (ADP-ribose) polymerase 1 1.616079 0.0046287 MFF mitochondrial fission factor 1.615445 0.04236204 C17orf28 Chromosome 17 open reading frame 28 1.615205 0.01857967 SSFA2 sperm specific antigen 2 1.613665 0.03156742 INTS10 integrator complex subunit 10 1.61321 0.03759633 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX41 4 1 1.613103 0.01994811 SP7 Sp7 transcription factor 1.612873 0.03503308 LOC348840 hypothetical LOC348840 1.612318 0.0333923 Clorf64 chromosome 1 open reading frame 64 1.61183 0.03787225 TD02 tryptophan 2,3-dioxygenase 1.611314 0.02656894 CAV1 caveolin 1, caveolae protein, 22kDa 1.611044 0.02082052 Williams-Beuren syndrome chromosome WBSCR28 region 28 1.610314 0.00484965 PCGF3 polycomb group ring finger 3 1.609233 0.04500391 LYPD1 LY6/PLAUR domain containing 1 1.60869 0.0035166 PTPRC protein tyrosine phosphatase, receptor type, C 1.608622 0.04671333 CSNK1G1 casein kinase 1, gamma 1 1.608354 0.02852645 Protein phosphatase 1, regulatory (inhibitor) PPP1R9B subunit 9B 1.608304 0.04955725 DNM2 dynamin 2 1.60777 0.00414141 DUSP1 dual specificity phosphatase 1 1.607697 0.04177325 solute carrier family 22 (organic anion SLC22A8 transporter), member 8 1.607396 0.00196477 MIT, microtubule interacting and transport, MITD1 domain containing 1 1.60683 0.04251328 ACHE acetylcholinesterase (Yt blood group) 1.606818 0.03555008 AMBRA1 autophagy/beclin- 1 regulator 1 1.60667 0.0180331 1 NT5C3 5'-nucleotidase, cytosolic III 1.606528 0.03931726 Clorf94 chromosome 1 open reading frame 94 1.606141 0.02028391 vacuolar protein sorting 4 homolog A (S. VPS4A cerevisiae) 1.606059 0.01278086 CHML choroideremia-like (Rab escort protein 2) 1.605833 0.00700314 LMNA lamin A/C 1.605628 0.03179212 NUP54 nucleoporin 54kDa 1.605456 0.01761976 HBP1 HMG-box transcription factor 1 1.605236 0.03723468 glutamate receptor, ionotropic, N-methyl D- aspartate-associated protein 1 (glutamate GRINA binding) 1.605053 0.02558557 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CYB5RL cytochrome b5 reductase-Hke 1.604601 0.04650936 glucocorticoid modulatory element binding GMEB2 protein 2 1.604463 0.0140619 xeroderma pigmentosum, complementation XPC group C 1.604321 0.02637103 PLXNB3 plexin B3 1.603875 0.03721121 C14orfl02 chromosome 14 open reading frame 102 1.603636 0.02439481 solute carrier family 30 (zinc transporter), SLC30A5 member 5 1.603386 0.01412032 lipid phosphate phosphatase-related protein LPPR2 type 2 1.602546 0.01890624 FLJ44653 shadow of prion protein pseudogene 1.602295 0.01487034 FXYD domain containing ion transport FXYD5 regulator 5 1.601868 0.02767412 NSUN2 NOP2/Sun domain family, member 2 1.601739 0.03789891 IMP (inosine 5'-monophosphate) IMPDH1 dehydrogenase 1 1.601557 0.02390004 RAD17 RAD17 homolog (S. pombe) 1.601375 0.0208996 MPG N-methylpurine-DNA glycosylase 1.601321 0.0278861 PDE4DIP phosphodiesterase 4D interacting protein 1.600681 0.03762262 AGTPBP1 ATP/GTP binding protein 1 1.600172 0.04242109 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q NDUFS1 reductase) 1.600136 0.00377063 KIAA1432 KIAA1432 1.599882 0.01279288 fibroblast growth factor (acidic) intracellular FIBP binding protein 1.599584 0.00865392 SDCBP2 syndecan binding protein (syntenin) 2 1.599528 0.04436837 TM9SF2 transmembrane 9 superfamily member 2 1.599129 0.0469163 serrate RNA effector molecule homolog SRRT (Arabidopsis) 1.598778 0.04748051 KIAA1804 mixed lineage kinase 4 1.5985 0.01465947 SRGAP3 SLIT-ROBO Rho GTPase activating protein 3 1.598109 0.02406393 DLG2 discs, large homolog 2 (Drosophila) 1.59803 0.04648955 PLN phospholamban 1.597774 0.03369263 BIN2 bridging integrator 2 1.596659 0.03630293 AUTS2 autism susceptibility candidate 2 1.596405 0.01840948 CFI complement factor I 1.596392 0.0081991 GTPase activating protein (SH3 domain) G3BP2 binding protein 2 1.595921 0.03007079 PI4KB phosphatidylinositol 4-kinase, catalytic, beta 1.595832 0.01455479 family with sequence similarity 74, member FAM174A A 1.59576 0.03603914 SNX13 sorting nexin 13 1.595744 0.03359426 STAG3 stromal antigen 3 1.595647 0.04932906 PRP8 pre-mRNA processing factor 8 PRPF8 homolog (S. cerevisiae) 1.595386 0.02456534 DOCK8 dedicator of cytokinesis 8 1.595294 0.02519439 WDR37 WD repeat domain 37 1.594727 0.00378112 CD 180 CD180 molecule 1.59426 0.00270468 DB1/ 69437 5 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value LRRC39 leucine rich repeat containing 39 0.04469574 HOXA3 homeobox A3 0.03851359 C3orf63 chromosome 3 open reading frame 63 0.04996988 NRG1 neuregulin 1 0.02057303 KDM4A lysine (K)-specific demethylase 4A 0.00806626 RARS arginyl-tRNA synthetase 0.02013136 heat shock protein family B (small), member HSPB11 11 0.04902965 UNQ3028 N/A 0.04928276 IQCB1 IQ motif containing Bl 0.03315168 hypoxia inducible factor 1, alpha subunit HIF1A (basic helix-loop-helix transcription factor) 1.591415 0.00884964 ArfGAP with GTPase domain, ankyrin repeat AGAP4 and PH domain 4 0.0332583 IFNAR2 interferon (alpha, beta and omega) receptor 2 0.00484284 WDR35 WD repeat domain 3 0.00790004 MTCH1 mitochondrial carrier homolog 1 (C. elegans) 0.04063505 CCDC54 coiled-coil domain containing 54 0.03288872 FAF2 Fas associated factor family member 2 0.0271 1297 oxidative stress induced growth inhibitor OSGIN2 family member 2 0.02519466 KIAA1949 KIAA1949 0.04098394 PADI1 peptidyl arginine deiminase, type I 0.04804845 calcium channel, voltage-dependent, P/Q CACNA1A type, alpha 1A subunit 1.58815 0.02091973 FERM, RhoGEF (ARHGEF) and pleckstrin FARP1 domain protein 1 (chondrocyte-derived) 0.04607572 C22orf34 chromosome 22 open reading frame 34 0.01101082 class II, major histocompatibility complex, CIITA transactivator .586799 0.02529807 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, TAF9 32kDa 1.586724 0.04658612 nuclear autoantigenic sperm protein (histone- NASP binding) 0.02198518 KIRREL2 Kin of IRRE like 2 (Drosophila) 0.01097234 FADS2 Fatty acid desaturase 2 0.00033349 NF1 neurofibromin 1 0.03828146 CTSA cathepsin A 0.04152232 P4HA1 prolyl 4-hydroxylase, alpha polypeptide I 0.02420803 RFC5 replication factor C (activator 1) 5, 36.5kDa 0.00493414 ZNF655 zinc finger protein 655 0.03282984 PRLH prolactin releasing hormone 0.03987318 CCDC146 coiled-coil domain containing 146 0.04435089 Bromodomain and WD repeat domain BRWD2 containing 2 0.01008763 BTN2A2 butyrophilin, subfamily 2, member A2 0.03770244 TRIM58 tripartite motif-containing 58 0.02235746 KLK15 Kallikrein-related peptidase 15 0.02715313 OARS glutaminyl-tRNA synthetase 0.0125861 1 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CXCR4 chemokine (C-X-C motif) receptor 4 1.580898 0.04082367 cytochrome P450, family 3, subfamily A, CYP3A4 polypeptide 4 1.580699 0.04268473 NBAS neuroblastoma amplified sequence 1.580693 0.00388638 Clorf87 chromosome 1 open reading frame 87 1.580614 0.00863699 EXOC3L2 exocyst complex component -like 2 1.580241 0.00834036 PTPRM protein tyrosine phosphatase, receptor type, M 1.580029 0.00732594 LIMD2 LIM domain containing 2 1.579849 0.03016734 Smg-5 homolog, nonsense mediated mRNA SMG5 decay factor (C. elegans) 1.579435 0.0010077 C21orf91 chromosome 2 1 open reading frame 9 1 1.579127 0.03847725 ZNF663 Zinc finger protein 663 1.578963 0.03550333 EIF2C2 eukaryotic translation initiation factor 2C, 2 1.578877 0.02885005 GPR1 13 G protein-coupled receptor 113 1.578257 0.03397636 LYPLA2 lysophospholipase II 1.577251 0.04735262 IQWD1 IQ motif and WD repeats 1 1.576988 0.01881598 membrane bound O-acyltransferase domain MBOAT 1 containing 1 1.57594 0.03236491 TTLL2 tubulin tyrosine ligase-like family, member 2 1.575766 0.0307972 ATPase, aminophospholipid transporter ATP8A1 (APLT), class I, type 8A, member 1 1.575492 0.01557476 Ras protein-specific guanine nucleotide- RASGRF2 releasing factor 2 1.575085 0.0447572 guanine nucleotide binding protein (G GNA1 1 protein), alpha 11 (Gq class) 1.575028 0.0024914 Olfactory receptor, family 52, subfamily B, OR52B6 member 6 1.57501 1 0.01759295 CDC42 binding protein kinase beta (DMPK- CDC42BPB like) 1.574939 0.00935113 CD300LG CD300 molecule-like family member g 1.574229 0.00222999 KNTC1 kinetochore associated 1 1.573628 0.03209189 DEPDC4 DEP domain containing 4 1.573049 0.03533614 SHQ1 SHQ1 homolog (S. cerevisiae) 1.572124 0.03773088 MACC1 metastasis associated in colon cancer 1 1.571743 0.03047397 GOLM1 golgi membrane protein 1 1.571733 0.01360222 LRRC37B2 leucine rich repeat containing 37, member B2 1.571699 0.02532213 COL5A2 collagen, type V, alpha 2 1.5714 0.0309551 TP53BP1 tumor protein p53 binding protein 1 1.571 121 0.03849533 C l or O chromosome open reading frame 90 1.57091 1 0.01054486 phospholipase C, beta 1 (phosphoinositide- PLCB1 specific) 1.569662 0.041 19316 ANKRD32 ankyrin repeat domain 32 1.569041 0.02424598 RBM34 RNA binding motif protein 34 1.568797 0.00559575 carboxyl ester lipase (bile salt-stimulated CEL lipase) 1.568045 0.03937509 ANXA1 annexin A l 1.567821 0.00977338 core 1 synthase, glycoprotein-N- acetylgalactosamine 3-beta- C1GALT1 galactosyltransferase, 1 1.567234 0.04435706 FAT1 FAT tumor suppressor homolog 1 1.566978 0.01950681 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value (Drosophila) general transcription factor IIIC, polypeptide GTF3C1 1, alpha 220kDa 1.565863 0.03390878 ATMIN ATM interactor 1.565673 0.02568693 PNPT1 polyribonucleotide nucleotidyltransferase 1 1.565445 0.03732588 transcription elongation factor B polypeptide TCEB3C 3C (elongin A3) 1.565293 0.04760489 KLK3 kallikrein-related peptidase 3 1.565237 0.01348915 potassium voltage-gated channel, subfamily KCNF1 F, member 1 1.564143 0.02834103 MTA2 metastasis associated 1 family, member 2 1.563827 0.01761642 CBR4 carbonyl reductase 4 1.563764 0.0326285 C14orfl59 chromosome 14 open reading frame 159 1.563717 0.00169098 INTS7 integrator complex subunit 7 1.563662 0.04482643 SFTPC surfactant protein C 1.562999 0.01436025 PDE10A phosphodiesterase 10A 1.562608 0.02091243 ZKSCAN5 zinc finger with KRAB and SCAN domains 5 1.562567 0.00508912 EMID1 EMI domain containing 1 1.562191 0.00782405 AMPH amphiphysin 1.562135 0.0154874 NPIP nuclear pore complex interacting protein 1.562071 0.01869195 MTMR10 myotubularin related protein 0 1.561932 0.0103955 damage-specific DNA binding protein 1, DDB1 127kDa 1.561316 0.00746873 GATAD2B GATA zinc finger domain containing 2B 1.560948 0.04069536 solute carrier family 12 (sodium/potassium/chloride transporters), SLC12A2 member 2 1.560775 0.02096845 PDLIM7 PDZ and LIM domain 7 (enigma) 1.560624 0.01849702 RNF38 ring finger protein 38 1.560505 0.03660505 NOTCH4 Notch homolog 4 (Drosophila) 1.560209 0.02750535 solute carrier family 6 (neurotransmitter SLC6A13 transporter, GABA), member 13 1.560159 0.02092643 ARL8A ADP-ribosylation factor-like 8A 1.55933 0.02476569 DIP2 disco-interacting protein 2 homolog C DIP2C (Drosophila) 1.559135 0.0306571 TBR1 T-box, brain, 1 1.558615 0.00973385 DOCK5 dedicator of cytokinesis 5 1.558612 0.0134413 family with sequence similarity 113, member FAM113A A 1.558557 0.03275575 ZBTB1 zinc finger and BTB domain containing 1 1.558397 0.00183477 KRT23 Keratin 23 (histone deacetylase inducible) 1.558175 0.0148528 DKFZp434Fl 42 hypothetical DKFZp434F142 1.558166 0.03025031 Clorf96 chromosome 1 open reading frame 96 1.557442 0.00313993 MICALCL MICAL C-terminal like 1.557271 0.02847193 ADAM metallopeptidase with ADAMTS20 thrombospondin type 1 motif, 20 1.557258 0.01814664 tumor necrosis factor (ligand) superfamily, TNFSF13 member 13 1.556484 0.03059729 CAPRJN1 cell cycle associated protein 1 1.556445 0.01908969 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value INPP5J inositol polyphosphate-5-phosphatase J 1.556265 0.0041265 Amyotrophic lateral sclerosis 2 (juvenile) ALS2CR1 chromosome region, candidate 11 1.555369 0.04529981 MAN1A1 mannosidase, alpha, class 1A, member 1 1.554765 0.01354809 EPB41L5 erythrocyte membrane protein band 4.1 like 5 1.554615 0.00348279 ZNF445 zinc finger protein 445 1.554576 0.01779286 EMCN endomucin 1.554188 0.03905193 MAP2 microtubule-associated protein 2 1.55383 0.03204381 DNA cross-link repair 1A (PS02 homolog, S. DCLRE1A cerevisiae) 1.553638 0.03995784 MFAP3 microfibrillar-associated protein 3 1.553195 0.04737588 RAVER 1 Ribonucleoprotein, PTB-binding 1 1.552791 0.00727941 NCAPG non-SMC condensin I complex, subunit G 1.552663 0.03554067 WDR41 WD repeat domain 4 1 1.551501 0.00269208 calcium homeostasis endoplasmic reticulum CHERP protein 1.551363 0.01319 DVL3 dishevelled, dsh homolog 3 (Drosophila) 1.551 189 0.03796681 FRAS1 Fraser syndrome 1 1.551065 0.00045573 ANKRD13D ankyrin repeat domain 13 family, member D 1.55101 1 0.00199369 DES desmin 1.549738 0.01271598 E2F5 E2F transcription factor 5, pl30-binding 1.549601 0.03693464 phosphatidylinositol-5 -phosphate 4-kinase, PIP4K2C type II, gamma 1.549431 0.03481636 ZDHHC3 zinc finger, DHHC-type containing 3 .549004 0.00761 689 UHRF1BP1L UHRF1 binding protein 1-like 1.548447 0.00697566 WDR49 WD repeat domain 49 1.548196 0.0134696 YTHDF3 YTH domain family, member 3 1.548102 0.02135835 Src homology 2 domain containing adaptor SHB protein B 1.547684 0.00084426 CLEC18C C-type lectin domain family 18, member C 1.547543 0.01 004 1 protein tyrosine phosphatase, non-receptor PTPN2 type 2 1.54739 0.02035435 ZNF354B zinc finger protein 354B 1.547163 0.01684084 ABHD3 abhydrolase domain containing 3 .547037 0.04585433 TSLP thymic stromal lymphopoietin 1.546812 0.0157549 ADAM metallopeptidase with ADAMTS9 thrombospondin type 1 motif, 9 1.5455 11 0.00347952 GRHL1 grainyhead-like 1 (Drosophila) 1.544812 0.04849137 AQR aquarius homolog (mouse) .54435 1 0.01005732 diacylglycerol O-acyltransferase homolog 1 DGAT1 (mouse) 1.54416 0.01906196 ORMDL1 ORMl-like 1 (S. cerevisiae) 1.54414 0.02275899 TBC1D21 TBC1 domain family, member 2 1 1.543774 0.04418519 NCR3 natural cytotoxicity triggering receptor 3 1.5434 1 0.02868302 PCDH1 protocadherin 1 1.543274 0.04368429 GPR56 G protein-coupled receptor 56 1.542173 0.04121757 CPT1A carnitine palmitoyltransferase 1A (liver) 1.541995 0.0455955 DNMBP dynamin binding protein 1.54178 0.01037482 NT5DC1 5'-nucleotidase domain containing 1 1.541535 0.01224804 BTNL8 butyrophilin-like 8 1.541439 0.00940871 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value PZP pregnancy-zone protein 0.04044797 RGAG1 retrotransposon gag domain containing 1 0.04310469 ZNF248 Zinc finger protein 248 0.03294884 Cas-Br-M (murine) ecotropic retroviral CBLB transforming sequence b 0.02728626 TMEM39A transmembrane protein 39A 0.02298178 glucosaminyl (N-acetyl) transferase 3, mucin GCNT3 type 0.04765364 MMP19 matrix metallopeptidase 19 0.02127341 C19orf55 chromosome 1 open reading frame 55 0.02031633 ZNF639 zinc finger protein 639 0.03676195 Zic family member 5 (odd-paired homolog, ZIC5 Drosophila) 0.00518347 TUFT1 tuftelin 1 0.04381 125 ALK anaplastic lymphoma receptor tyrosine kinase 0.03566215 FCH02 FCH domain only 2 0.00085839 NFIA nuclear factor I/A 0.04313686 PAK2 p 1 protein (Cdc42/Rac)-activated kinase 2 0.03014228 UIMC1 ubiquitin interaction motif containing 1 0.01 11732 MANEAL mannosidase, endo-alpha-like 0.00444797 PSD3 pleckstrin and Sec7 domain containing 3 0.04330975 ATF6B activating transcription factor 6 beta 0.03667598 IP6K2 inositol hexakisphosphate kinase 2 0.01536192 mitogen-activated protein kinase 8 interacting MAPK8IP3 protein 3 0.00633798 ZBTB9 zinc finger and BTB domain containing 9 0.01918224 Stress-associated endoplasmic reticulum SERP1 protein 1 0.00112698 UBA2 ubiquitin-like modifier activating enzyme 2 0.03719408 C orf33 chromosome 15 open reading frame 33 0.03807529 inhibitor of CDK, cyclin Al interacting INCA1 protein 1 0.04573421 SFT2D3 SFT2 domain containing 3 0.03043152 DPEP3 dipeptidase 3 0.01954245 HEG1 HEG homolog 1 (zebrafish) 0.0324556 GLOl glyoxalase I 0.04519109 UTP15, U3 small nucleolar UTP15 ribonucleoprotein, homolog (S. cerevisiae) 0.01108262 C19orf50 chromosome 19 open reading frame 50 0.02943876 ARSF arylsulfatase F 0.0186262 transforming growth factor beta 1 induced TGFB1I1 transcript 1 1.533844 0.04888081 protein disulfide isomerase family A, member PDIA6 6 0.01326546 PPA2 pyrophosphatase (inorganic) 2 0.01586952 CDK5RAP3 CDK5 regulatory subunit associated protein 3 0.02254633 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- GALNTL4 acetylgalactosaminyltransferase-like 4 0.04491059 RTEL1 regulator of telomere elongation helicase 1 0.01527838 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value BCL9L B-cell CLL/lymphoma 9-like 1.531991 0.0045904 GBAS glioblastoma amplified sequence 1.531988 0.00296838 NCOA3 nuclear receptor coactivator 3 1.531259 0.00465947 ROPN1L ropporin 1-like 1.530537 0.01 192305 CXorf23 chromosome X open reading frame 23 .53043 0.03105831 APOA2 apolipoprotein A-II 1.53024 0.03723402 ACADVL acyl-CoA dehydrogenase, very long chain 1.529945 0.02404657 integrin, alpha V (vitronectin receptor, alpha ITGAV polypeptide, antigen CD51) 1.52992 1 0.02992868 ZNF672 zinc finger protein 672 1.529868 0.01291179 C9orfl 50 chromosome 9 open reading frame 150 1.529094 0.0151 1257 SSPO SCO-spondin homolog (Bos taurus) 1.529074 0.04138227 RGS7 regulator of G-protein signaling 7 1.528987 0.01630161 HAUS4 HAUS augmin-like complex, subunit 4 1.528799 0.04476215 CALCR calcitonin receptor 1.528616 0.00181452 SPATA3 Spermatogenesis associated 3 1.528332 0.00385196 LCLAT1 lysocardiolipin acyltransferase 1 1.527877 0.04339041 STK1 7B serine/threonine kinase 17b 1.52771 9 0.03760197 Clorfl98 chromosome 1 open reading frame 198 1.527608 0.01535303 AFF4 AF4/FMR2 family, member 4 1.52732 1 0.02022046 C3orfl5 chromosome 3 open reading frame 15 1.52695 0.04424073 GTPBP8 GTP-binding protein 8 (putative) .526699 0.02764528 cleft lip and palate associated transmembrane CLPTM1 protein 1 1.526502 0.03479322 solute carrier family 4, sodium bicarbonate SLC4A10 transporter, member 10 1.526501 0.04084261 MKRN3 makorin ring finger protein 3 1.526045 0.0085596 PIM1 pirn- 1 oncogene 1.525922 0.0424031 RAB23 RAB23, member RAS oncogene family 1.52539 0.01869873 ZFY zinc finger protein, Y-linked 1.525336 0.0029304 PCSK7 proprotein convertase subtilisin/kexin type 7 1.525 15 0.00584015 phospholipase A2, group IVC (cytosolic, PLA2G4C calcium-independent) 1.52491 0.02842672 KIAA1279 KIAA1279 1.524763 0.01 136681 ANKRD35 ankyrin repeat domain 35 1.524669 0.02594497 UDP glucuronosyltransferase 1 family, UGT1A7 polypeptide A7 1.524507 0.04652272 Usher syndrome 1C (autosomal recessive, USH1C severe) 1.524293 0.00891889 CDC42SE1 CDC42 small effector 1 1.524227 0.02124608 MKRN2 makorin ring finger protein 2 1.524163 0.04756701 LAS1L LASl-like (S. cerevisiae) 1.523924 0.0047693 WDR66 WD repeat domain 66 1.523336 0.03741995 RICH2 Rho-type GTPase-activating protein RICH2 1.5233 16 0.00911856 FAM76B family with sequence similarity 76, member B 1.523274 0.03193599 ZNF616 zinc fmger protein 616 1.523196 0.01759284 FZD10 frizzled homolog 10 (Drosophila) 1.523097 0.03396822 nuclear factor of kappa light polypeptide gene NFKBIZ enhancer in B-cells inhibitor, zeta 1.522876 0.01551464 KLHDC2 kelch domain containing 2 1.5223 13 0.02042568 1/ 694375 16. 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value IRAKI interleukin-1 receptor-associated kinase 1 1.522241 0.00602997 FANCA Fanconi anemia, complementation group A 1.522057 0.02479576 TNS1 tensin 1 1.521956 0.03592733 inner centromere protein antigens INCENP 135/155kDa 1.521596 0.00926599 Ral GEF with PH domain and SH3 binding RALGPS2 motif 2 1.521416 0.00618193 GPR128 G protein-coupled receptor 128 1.520965 0.00372652 FLJ37396 hypothetical protein FL.T37396 1.520372 0.04538205 SP140L SP140 nuclear body protein-like 1.520204 0.02461727 ACVR2A activin A receptor, type IIA 1.519658 0.0083885 GLT25D2 glycosyltransferase 25 domain containing 2 1.519436 0.03927104 C2orf63 chromosome 2 open reading frame 63 1.519398 0.00148009 DYNC1H1 dynein, cytoplasmic 1, heavy chain 1 1.519287 0.02522096 PMSl postmeiotic segregation increased 1 (S. PMSl cerevisiae) 1.51918 0.04248844 KIAA1324 KIAA1324 1.518936 0.03849599 C21orf90 chromosome 1 open reading frame 90 1.518365 0.03883319 ATPase, H+ transporting, lysosomal V0 ATP6V0A4 subunit a4 1.518126 9.30E-06 HIG1 hypoxia inducible domain family, HIGD1A member 1A 1.518117 0.0008097 solute carrier family 6 (neurotransmitter SLC6A4 transporter, serotonin), member 4 1.517608 0.03883098 mannosyl (alpha-l,3-)-glycoprotein beta-1,4- MGAT4A N-acetylglucosaminyltransferase, isozyme A 1.517593 0.01744339 CDP-diacylglycerol—inositol 3- CDIPT phosphatidyltransferase 1.517408 0.0451 1741 colony stimulating factor 2 receptor, beta, CSF2RB low-affinity (granulocyte-macrophage) 1.517362 0.04008848 HOXA9 homeobox A9 1.517045 0.04696364 MAN2A1 mannosidase, alpha, class 2A, member 1 1.516951 0.0270042 family with sequence similarity 82, member FAM82A1 A l 1.516347 0.01479676 ETV5 ets variant 5 1.516057 0.04481994 RPS10 ribosomal protein S 0 1.516017 0.02906973 aldehyde dehydrogenase 8 family, member ALDH8A1 A l 1.515699 0.03066374 TMEM48 transmembrane protein 48 1.514852 0.04795775 glutamate decarboxylase 2 (pancreatic islets GAD2 and brain, 65kDa) 1.514642 0.03182126 PCDH15 Protocadherin 1 1.514612 0.04382075 transmembrane emp24 protein transport TMED4 domain containing 4 1.514565 0.04591312 calcium channel, voltage-dependent, alpha CACNA2D1 2/delta subunit 1 1.514413 0.00568028 ALPL alkaline phosphatase, liver/bone/kidney 1.514321 0.0280432 TGM6 transglutaminase 6 1.514171 0.02168385 KIAA1109 KIAA1109 1.51414 0.01690086 PARP9 poly (ADP-ribose) polymerase family, 1.513927 0.03008991 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value member 9 olfactory receptor, family 5, subfamily I, OR5I1 member 1 1.51391 0.03273026 FBN3 Fibrillin 3 1.513639 0.03689208 ribosomal protein S6 kinase, 90kDa, RPS6KA3 polypeptide 3 1.513578 0.04127709 non-metastatic cells 7, protein expressed in N E7 (nucleoside-diphosphate kinase) 1.513493 0.01033888 WDR36 WD repeat domain 36 1.51338 0.03790186 IFRD1 interferon-related developmental regulator 1 1.512674 0.02802167 GM2A GM2 ganglioside activator 1.512602 0.03087316 MCPH1 Microcephalin 1 1.512198 0.02307828 RNF207 ring finger protein 207 1.51 1946 0.006231 1 IQSEC1 IQ motif and Sec7 domain 1 1.51151 0.02037703 UDP glucuronosyltransferase 1 family, UGT1A9 polypeptide A9 1.511159 0.02271588 POLQ polymerase (DNA directed), theta 1.510962 0.03235888 MRPS33 mitochondrial ribosomal protein S33 1.510729 0.02680392 DYX1C1 dyslexia susceptibility 1 candidate 1 1.510621 0.01800952 TREXl Three prime repair exonuclease 1 1.510618 0.0479416 POMT2 protein-O-mannosyltransferase 2 1.510577 0.02206787 MAP7 microtubule-associated protein 7 1.51051 0.04421807 GPATCH4 G patch domain containing 4 1.510344 0.03298126 MTA1 metastasis associated 1 1.510324 0.02069066 Clorfl75 chromosome 1 open reading frame 175 1.510261 0.03674759 C5orf4 chromosome 5 open reading frame 4 1.509893 0.03555095 calcium/calmodulin-dependent serine protein CASK kinase (MAGUK family) 1.509852 0.02504441 FLJ33534 hypothetical LOC285 150 1.509641 0.00605129 SUSD1 sushi domain containing 1 1.509077 0.001 10171 MED12L mediator complex subunit 12-like 1.50899 0.00845126 ATP-binding cassette, sub-family A (ABCl), ABCA4 member 4 1.508877 0.0360565 CTPS CTP synthase 1.508758 0.03235272 UGP2 UDP -glucose pyrophosphorylase 2 1.50845 0.04195768 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 14 (GalNAc- GALNT14 T14) 1.508233 0.00975996 C16orf82 chromosome 16 open reading frame 82 1.508071 0.01412293 ZMYND8 zinc finger, MYND-type containing 8 1.507935 0.0154587 GBA glucosidase, beta, acid 1.507121 0.0186475 MANSC1 MANSC domain containing 1 1.506913 0.03010828 MBD1 methyl-CpG binding domain protein 1 1.506387 0.01403498 C7orf50 chromosome 7 open reading frame 50 1.505924 0.01 147375 NIMA (never in mitosis gene a)-related NEK1 kinase 1 1.505029 0.00488555 TAF1 R A polymerase II, TATA box binding protein (TBP)-associated factor, TAF1 1 28kDa 1.504602 0.04250863 B 1/ 694375 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ST7L suppression of tumorigenicity 7 like 0.01399733 DNAH9 dynein, axonemal, heavy chain 9 0.04054231 TNP02 transportin 2 0.00026096 PSD4 pleckstrin and Sec7 domain containing 4 0.04978432 ABLIM3 actin binding LIM protein family, member 3 0.0297663 C6orfl42 chromosome 6 open reading frame 142 0.01949794 sulfotransferase family, cytosolic, 1A, phenol- SULT1A3 preferring, member 3 0.04257144 CAPN3 calpain 3, (p94) 0.01986647 thymocyte selection-associated high mobility TOX group box 0.02915765 ZNF205 zinc finger protein 205 0.00100172 chymotrypsin-like elastase family, member CELA2A 2A 0.00239408 DLX5 distal-less homeobox 5 0.00306021 CCDC88A coiled-coil domain containing 88A 0.04767025 STOML1 stomatin (EPB72)-like 1 0.0280494 MID2 midline 2 0.0169234 CSGLCA-T Chondroitin sulfate glucuronyltransferase 0.01010816 P4HA2 prolyl 4-hydroxylase, alpha polypeptide II 0.0292032 MY06 myosin VI 0.04628552 GEMIN8 gem (nuclear organelle) associated protein 8 0.01700446 RNASEH2B ribonuclease H2, subunit B 0.02568195 solute carrier family 2 (potassium/chloride SLC12A5 transporter), member 5 1.498932 0.04182994 cytochrome P450, family 20, subfamily A, CYP20A1 polypeptide 1 0.00860486 BPTF bromodomain PHD finger transcription factor 0.0230048 PHTF2 Putative homeodomain transcription factor 2 0.01305125 ZBTB7A zinc finger and BTB domain containing 7A 0.01 106742 PDK1 pyruvate dehydrogenase kinase, isozyme 1 0.0151 1556 KRTAPlO-10 keratin associated protein 10-10 0.01929623 SAP130 Sin3A-associated protein, 130kDa 0.0309965 C20orfl 1 chromosome 20 open reading frame 11 0.03218343 GPR162 G protein-coupled receptor 162 0.00727074 ArfGAP with RhoGAP domain, ankyrin ARAP3 repeat and PH domain 3 0.03446676 FAM120B family with sequence similarity 120B 0.02053027 protein kinase, DNA-activated, catalytic PRKDC polypeptide 1.496476 0.04042323 actin related protein 2/3 complex, subunit 1A, ARPC1A 41kDa 0.0273321 ATPase, Na+/K+ transporting, alpha 4 ATP1A4 polypeptide 0.00959306 TESSP2 Testis serine protease 2 0.04986434 ARHGDIB Rho GDP dissociation inhibitor (GDI) beta 0.04171769 TBC1D5 TBC1 domain family, member 5 0.04532486 SLTM SAFB-like, transcription modulator 0.02071 192 ALPK1 alpha-kinase 1 0.00084307 SLC37A1 solute carrier family 37 (glycerol-3-phosphate 0.00887469 DB1/ 69 37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value transporter), member 1 VAV3 vav 3 guanine nucleotide exchange factor 1.49455 0.00863513 calcium channel, voltage-dependent, L type, CACNA1D alpha ID subunit 1.494529 0.04770073 C17orf39 chromosome 17 open reading frame 39 1.494082 0.02305828 ventricular zone expressed PH domain VEPH1 homolog 1 (zebrafish) 1.493979 0.00237279 VDAC1 voltage-dependent anion channel 1 1.493692 0.00815443 GADD45GIP growth arrest and DNA-damage-inducible, 1 gamma interacting protein 1 1.493655 0.02061236 GRN granulin 1.493607 0.03683456 IDUA iduronidase, alpha-L- 1.493505 0.00362299 olfactory receptor, family 11, subfamily H, OR11H1 member 1 1.493333 0.02470052 EYA2 eyes absent homolog 2 (Drosophila) 1.492952 0.04100083 CCDC123 coiled-coil domain containing 1 3 1.492601 0.0041 1613 solute carrier family 35 (CMP-sialic acid SLC35A1 transporter), member 1.492421 0.03009839 SLC25A37 solute carrier family 25, member 37 1.492148 0.02969246 tumor necrosis factor receptor superfamily, TNFRSF10B member 10b 1.492041 0.0473876 CUGBP2 CUG triplet repeat, R A binding protein 2 1.491452 0.00976238 FBX042 F-box protein 42 1.491338 0.03781683 WDYHV1 WDYHV motif containing 1 1.491315 0.0290555 TLR9 toll-like receptor 9 1.491057 0.02533605 STRN3 striatin, calmodulin binding protein 3 1.490937 0.04429151 JRKL jerky homolog-like (mouse) 1.490843 0.03773327 WDR65 WD repeat domain 65 1.489954 0.02181211 ubiquinol-cytochrome c reductase, Rieske UQCRFS1 iron-sulfur polypeptide 1 1.489845 0.02452908 ASPN asporin 1.489751 0.02227567 L3MBTL2 l(3)mbt-like 2 (Drosophila) 1.489618 0.00853662 HESX1 HESX homeobox 1 1.48897 0.01313614 upstream transcription factor 2, c-fos USF2 interacting 1.488893 0.02332004 RIT1 Ras-like without CAAX 1 1.488704 0.01691638 CXCR7 chemokine (C-X-C motif) receptor 7 1.48836 0.04469999 solute carrier family 3 (cystine, dibasic and neutral amino acid transporters, activator of cystine, dibasic and neutral amino acid SLC3A1 transport), member 1 1.488117 0.00445729 CI lor© chromosome 1 open reading frame 9 1.487813 0.04541662 CSAD cysteine sulfinic acid decarboxylase 1.487784 0.04360266 N4BP2 NEDD4 binding protein 2 1.487665 0.04561429 BMPR1B bone morphogenetic protein receptor, type IB 1.487422 0.01325305 MY015B Myosin XVB pseudogene 1.487292 0.03221572 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX20 20 1.487244 0.0038332 phosphatidylinositol-3,4,5-trisphosphate- PREX2 dependent Rac exchange factor 2 1.486892 0.02762766 DBl/ 694375] 6.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value E2F6 E2F transcription factor 6 0.04873563 CCDC38 coiled-coil domain containing 38 0.04585151 C9 complement component 9 0.03138149 ILK integrin-linked kinase 0.03627245 AD54L RAD54-like (S. cerevisiae) 0.00858123 LAMB1 laminin, beta 1 0.00653142 CIB1 calcium and integrin binding 1 (calmyrin) 0.01107503 HIST1H2AC histone cluster 1, H2ac 0.02826414 KIAA0319L KIAA0319-like 0.00321669 KIF5C kinesin family member 5C 0.03417717 GSK3A glycogen synthase kinase 3 alpha 0.01 122827 KDM6A lysine (K)-specific demethylase 6A 0.02741398 GUSB glucuronidase, beta 0.00747287 QPCT glutaminyl-peptide cyclotransferase 0.04104095 BCAS4 breast carcinoma amplified sequence 4 0.02197508 BTN2A1 butyrophilin, subfamily 2, member Al 0.00038605 SYCP1 synaptonemal complex protein 1 0.04266731 KRBA1 KRAB-A domain containing 1 0.00220749 poly (ADP-ribose) polymerase family, PARP4 member 4 0.00301927 SI 2 single-minded homolog 2 (Drosophila) 0.04804004 ATRNL1 attractin-like 1 0.03262769 SWI/SNF related matrix associated, actin dependent regulator of chromatin, subfamily SMARCB1 b, member 1 0.01 17909 ZZEF1 zinc finger, ZZ-type with EF-hand domain 1 0.02785441 pseudouridylate synthase 7 homolog (S. PUS7 cerevisiae) 0.04277312 KDM4B lysine (K)-specific demethylase 4B 0.0292299 ZNF238 zinc finger protein 238 0.01726056 transglutaminase 3 (E polypeptide, protein- TGM3 glutamine-gamma-glutamyltransferase) 0.02530872 ERGIC3 ERGIC and golgi 3 0.00847787 SLC41A3 solute carrier family 41, member 3 0.03315266 integrin, alpha 5 (fibronectin receptor, alpha ITGA5 polypeptide) 0.01069824 NSBP1 Nucleosomal binding protein 1 0.03963054 NAV1 neuron navigator 1 0.0407588 FOSL2 FOS-like antigen 2 0.00031436 nuclear factor of kappa light polypeptide gene NFKBID enhancer in B-cells inhibitor, delta 0.00732586 GGT1 gamma-glutamyltransferase 1 0.00264442 DOCK3 dedicator of cytokinesis 3 0.04456291 POU5F1 POU class 5 homeobox 1 0.0205725 ZNF776 zinc finger protein 776 0.01308106 PCTK3 PCTAIRE protein kinase 3 0.04215809 family with sequence similarity 171, member FAM171B B 0.01422667 phosphoinositide-3 -kinase, regulatory subunit PIK3R4 4 0.04851308 DBl/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value MED23 mediator complex subunit 23 0.04028339 LPIN2 lipin 2 0.04844938 PIAS2 protein inhibitor of activated STAT, 2 0.02186057 ZNF346 zinc finger protein 346 0.011 12805 CCNL2 cyclin L2 0.02934899 ZNF317 Zinc finger protein 317 0.02908138 CUBN cubilin (intrinsic factor-cobalamin receptor) 0.03940218 ZNF669 zinc finger protein 669 0.008801 1 LRRC28 leucine rich repeat containing 28 0.04717917 signal transducer and activator of STAT2 transcription 2, 113kDa 0.00464306 KATNAl katanin p60 (ATPase-containing) subunit A 1 0.03371068 KIAA1407 KIAA1407 0.04081785 PCID2 PCI domain containing 2 0.02600855 E 0 1LB EROl-like beta (S. cerevisiae) 0.02510508 HEATR7B2 HEAT repeat family member 7B2 0.0474 PTGR2 prostaglandin reductase 2 0.01576499 EP300 E lA binding protein p300 0.03674569 sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, SEMA5A (semaphorin) 5A 0.03564324 TYSND1 trypsin domain containing 1 0.03841 107 FASTKD1 FAST kinase domains 1 0.01426259 nucleotide-binding oligomerization domain NOD2 containing 2 0.00327639 RNF167 ring finger protein 67 0.031 12976 DEAH (Asp-Glu-Ala-His) box polypeptide DHX29 29 0.01019979 GSDMD gasdermin D 0.04369056 Microtubule-associated protein 1 light chain 3 MAP1LC3A alpha 0.04249948 TEAD3 TEA domain family member 3 0.03096314 family with sequence similarity 126, member FAM126B B 0.03569178 LIPA lipase A, lysosomal acid, cholesterol esterase 0.02558128 advanced glycosylation end product-specific AGER receptor 0.03465146 phytanoyl-CoA 2-hydroxylase interacting PHYHIPL protein-like 0.02514305 solute carrier organic anion transporter SLC04C1 family, member 4C 1 0.01 184326 LDHD lactate dehydrogenase D 0.00975421 KRT28 keratin 28 0.01816292 IQ motif containing GTPase activating IQGAP3 protein 3 0.01554435 nudix (nucleoside diphosphate linked moiety NUDT3 X)-type motif 3 0.00899816 coiled-coil-helix-coiled-coil-helix domain CHCHD2 containing 2 0.01172654 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P value ARHGAP9 Rho GTPase activating protein 9 1.466942 0.0280099 Family with sequence similarity 62 (C2 FAM62B domain containing) member B 1.466889 0.01377577 GCLC glutamate-cysteine ligase, catalytic subunit 1.466645 0.02679587 ARR3 arrestin 3, retinal (X-arrestin) 1.466048 0.01696652 regulator of G protein signaling 9 binding RGS9BP protein 1.465883 0.03961413 phospholipase A2, group VI (cytosolic, PLA2G6 calcium-independent) 1.465765 0.02742349 BAALC Brain and acute leukemia, cytoplasmic 1.46535 0.00024952 LRRN4 leucine rich repeat neuronal 4 1.465336 0.00738088 EXD3 exonuclease 3'-5' domain containing 3 1.464634 0.02526724 insulin-like growth factor 2 mRNA binding IGF2BP2 protein 2 1.464327 0.04162595 FOXQ1 forkhead box Q 1.464178 0.00212678 solute carrier family 39 (zinc transporter), SLC39A13 member 13 1.464156 0.01844752 RASA2 RAS p21 protein activator 2 1.463718 0.00740884 KIF16B kinesin family member 16B 1.463596 0.011 15288 KRTAP10-8 keratin associated protein 10-8 1.463269 0.000559 CRTC2 CREB regulated transcription coactivator 2 1.463094 0.04358035 protein phosphatase, Mg2+/Mn2+ dependent, PPM1H 1H 1.462605 0.01356042 S100A16 S 00 calcium binding protein A 6 1.462571 0.04659033 TBL1X transducin (beta)-like lX-linked 1.462548 0.02846753 ZNF35 zinc finger protein 35 1.462328 0.01374461 peptidase domain containing associated with PAMR1 muscle regeneration 1 1.461975 0.0389447 ADCY5 adenylate cyclase 5 1.461874 0.01746332 X-prolyl aminopeptidase (aminopeptidase P) XPNPEP2 2, membrane-bound 1.461415 0.02555418 dual-specificity tyrosine-(Y)-phosphorylation DYRK1A regulated kinase 1A 1.461295 0.02525277 cytochrome P450, family 3, subfamily A, CYP3A7 polypeptide 7 1.461 141 0.03694454 MAPK14 mitogen-activated protein kinase 14 1.461055 0.00495656 NBEA neurobeachin 1.460973 0.03240274 C7orf42 chromosome 7 open reading frame 42 1.460876 0.02721132 semaphorin 7A, GPI membrane anchor (John SEMA7A Milton Hagen blood group) 1.460443 0.04669342 RUNX1 runt-related transcription factor 1 1.46004 0.04954951 P1POX pipecolic acid oxidase 1.459566 0.01220641 COL16A1 collagen, type XVI, alpha 1 1.459324 0.00255753 CCDC155 coiled-coil domain containing 155 1.459029 0.00173523 ELSPBP1 epididymal sperm binding protein 1 1.458425 0.04218641 PRDM14 PR domain containing 14 1.458395 0.04902037 thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, THRB avian) 1.457783 0.02863261 UHRF1BP1 UHRF1 binding protein 1 1.457743 0.04933297 B / 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ATP synthase mitochondrial F l complex ATPAF2 assembly factor 2 0.04978588 UCK1 uridine-cytidine kinase 1 0.02615271 SPTBN2 spectrin, beta, non-erythrocytic 2 0.01348539 fumarylacetoacetate hydrolase FAH (fumarylacetoacetase) 0.03082082 CCDC78 coiled-coil domain containing 78 0.00779009 protein kinase, AMP-activated, beta 1 non- PRKAB1 catalytic subunit 1.456934 0.00674298 NADH dehydrogenase (ubiquinone) 1 alpha NDUFA13 subcomplex, 13 0.04645714 KAT2A K(lysine) acetyltransferase 2A 0.00222147 RPL28 ribosomal protein L28 0.03220045 mannosyl (alpha-l,3-)-glycoprotein beta- 1,4- MGAT4B N-acetylglucosaminyltransferase, isozyme B 0.04076649 FBN1 fibrillin 1 0.02322272 ULK4 unc-51-like kinase 4 (C. elegans) 0.04272579 X-linked Kx blood group (McLeod XK syndrome) 0.02239272 UPK2 uroplakin 2 0.04753193 CEP68 centrosomal protein 68kDa 0.03508992 platelet-derived growth factor receptor, alpha PDGFRA polypeptide 0.0179518 USP51 Ubiquitin specific peptidase 5 0.03331 138 Sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, SEMA5B (semaphorin) 5B 1.454976 0.02313882 elongation factor Tu GTP binding domain EFTUD2 containing 2 0.01886939 FR D4A FEPvM domain containing 4A 0.01579827 UHM 1 U2AF homology motif (UHM) kinase 1 0.03607354 DMXL2 Dmx-like 2 0.00874766 ZW T ZW10 interactor 0.00942131 OSBP oxysterol binding protein 0.04350568 SBF2 SET binding factor 2 0.01078788 C12orf48 chromosome 1 open reading frame 48 0.02655996 SLC15A3 solute carrier family 15, member 3 0.0045492 CAPSL calcyphosine-like 0.02075975 FBXL17 F-box and leucine-rich repeat protein 7 0.03278551 C2orf53 chromosome 2 open reading frame 53 0.04970591 SRR serine racemase 0.03543625 EDN2 endothelin 2 0.03828423 cAMP responsive element binding protein 3- CREB3L2 like 2 0.02761724 vacuolar protein sorting 33 homolog A (S. VPS33A cerevisiae) 0.03534595 calmodulin regulated spectrin-associated CAMSAPI protein 1 0.03807689 ADCY2 Adenylate cyclase 2 (brain) 0.02341994 1/ 6943 7516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value 1-aminocyclopropane-l -carboxylate synthase ACCS homolog (Arabidopsis)(non-functional) 1.450606 0.0041 161 1 SRM spermidine synthase 1.450314 0.0386075 KIF1B kinesin family member IB 1.450105 0.00795995 CLINT1 clathrin interactor 1 1.450089 0.03162318 HERC2P2 Hect domain and RLD 2 pseudogene 2 1.449895 0.03248465 protein phosphatase 1, regulatory (inhibitor) PPP1R3D subunit 3D 1.449813 0.02244246 Plectin 1, intermediate filament binding PLEC1 protein 500kDa 1.449738 0.04213924 Clorf92 chromosome 1 open reading frame 92 1.44966 0.01543183 FLCN folliculin 1.449054 0.0230347 BRD7 bromodomain containing 7 1.448578 0.00933436 postmeiotic segregation increased 2-like 2 PMS2L2 pseudogene 1.448546 0.005051 12 NCR1 natural cytotoxicity triggering receptor 1 1.448542 0.04855739 C10orfl04 Chromosome 10 open reading frame 104 1.448491 0.00267935 SSPN sarcospan (Kras oncogene-associated gene) 1.44845 0.03302467 RNA pseudouridylate synthase domain RPUSD3 containing 3 1.448408 0.00998086 DRP2 dystrophin related protein 2 1.448236 0.00721484 latent transforming growth factor beta binding LTBP2 protein 2 1.448086 0.02740361 TMEM14C transmembrane protein C 1.447908 0.01223887 aldehyde dehydrogenase 1 family, member ALDH1L1 LI 1.447745 0.03397317 SMC B structural maintenance of chromosomes 1.447653 0.01700052 CCDC45 coiled-coil domain containing 45 1.447508 0.01 193568 FRMD6 FERM domain containing 6 1.447341 0.04706103 TRIM27 tripartite motif-containing 27 1.447185 0.04931 29 JMJD4 jumonji domain containing 4 1.446898 0.01389272 LEMD3 LEM domain containing 3 1.44673 0.04092375 ANXA6 annexin A6 1.446179 0.02394412 Olfactory receptor, family 2, subfamily W, OR2W3 member 3 1.445748 0.02959812 tRNA methyltransferase 6 1 homolog B (S. TRMT61B cerevisiae) 1.445655 0.04102036 C22orf24 chromosome 22 open reading frame 24 1.445618 0.04413586 SYCP2 synaptonemal complex protein 2 1.44557 0.01896128 UNC5C unc-5 homolog C (C. elegans) 1.445531 0.03566415 ADRBK1 adrenergic, beta, receptor kinase 1 1.445273 0.03231885 antagonist of mitotic exit network 1 homolog AMN1 (S. cerevisiae) 1.445051 0.033402 RBPMS RNA binding protein with multiple splicing 1.44501 0.03858333 BMP6 bone morphogenetic protein 6 1.444856 0.02522336 IKZF4 IKAROS family zinc finger 4 (Eos) 1.444792 0.04121343 HEATR3 HEAT repeat containing 3 1.444721 0.0101094 LOXHD1 lipoxygenase homology domains 1 1.4447 0.00078933 DGKH Diacylglycerol kinase, eta 1.444408 0.0205564 KIAA1191 KIAA1191 1.444339 0.03985924 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SPATA7 spermatogenesis associated 7 1.444215 0.01031062 transmembrane and tetratricopeptide repeat TMTC4 containing 4 1.443929 0.02091397 SEC24C SEC24 family, member C (S. cerevisiae) 1.443774 0.031 13679 LOC400940 hypothetical LOC400940 1.443742 0.04018813 sodium channel, voltage-gated, type XI, alpha SCN1 1A subunit 1.44344 0.0435613 translocase of outer mitochondrial membrane TOMM70A 70 homolog A (S. cerevisiae) 1.442531 0.03272251 toll-interleukin 1 receptor (TIR) domain TIRAP containing adaptor protein 1.442305 0.0353389 MAML1 mastermind-like 1 (Drosophila) 1.442288 0.03228402 family with sequence similarity 115, member FAM1 15C C 1.442232 0.03824025 SIGLEC9 sialic acid binding Ig-like lectin 9 1.442189 0.00149336 C15orf41 chromosome 5 open reading frame 4 1 1.442137 0.04387507 SMAD1 SMAD family member 1 1.442081 0.01612332 DMC1 dosage suppressor of mckl homolog, meiosis-specific homologous recombination DMC1 (yeast) 1.441914 0.01212361 SLC35B3 solute carrier family 35, member B3 1.441522 0.0071 1122 Cytochrome P450, family 2, subfamily C, CYP2C19 polypeptide 19 1.441363 0.0170018 MOGAT3 monoacylglycerol O-acyltransferase 3 1.441283 0.03555083 mitochondrial carrier triple repeat 1 LOC494141 pseudogene 1.441004 0.01257991 UBXN10 UBX domain protein 10 1.440741 0.00806327 Clorf65 chromosome 1 open reading frame 65 1.440539 0.04575707 CRIP2 cysteine-rich protein 2 1.440525 0.03552207 CFB complement factor B 1.440334 0.02702825 C16orf45 chromosome 16 open reading frame 45 1.440058 0.01337094 CKLF chemokine-like factor 1.440038 0.04099922 MORN! MORN repeat containing 1 1.439966 0.04582123 KIAA0125 KIAA0125 1.43966 0.04041667 GEMIN5 gem (nuclear organelle) associated protein 5 1.439594 0.0397608 tRNA splicing endonuclease 54 homolog (S. TSEN54 cerevisiae) 1.439572 0.04851051 REPS1 RALBPl associated Eps domain containing 1 1.439539 0.0313097 CSMD2 CUB and Sushi multiple domains 2 1.439487 0.00017482 eukaryotic translation elongation factor 1 EEF1A1 alpha 1 1.439448 0.03794699 MCHR1 melanin-concentrating hormone receptor 1 1.439291 0.00549179 NKX3-1 NK3 homeobox 1 1.439246 0.00916252 protein C (inactivator of coagulation factors PROC Va and Villa) 1.439197 0.03744441 14-Sep N/A 1.439028 0.02172227 Neural precursor cell expressed, NEDD4L developmentally down-regulated 4-like 1.438929 0.03498104 protein phosphatase 1, regulatory (inhibitor) PPP1R14D subunit 14D 1.438585 0.03281531 )B 1/ 694375 16.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value solute carrier family 2 (sodium/potassium/chloride transporters), SLC12A1 member 1 1.4381 16 0.02379177 PSG2 pregnancy specific beta- 1-glycoprotein 2 1.437935 0.04206079 DPT dermatopontin 1.437896 0.04729978 ARMC9 armadillo repeat containing 9 1.437839 0.02857529 EPAS1 endothelial PAS domain protein 1 1.437838 0.02537747 ATL1 atlastin GTPase 1 1.437797 0.02539355 ZNF 1 Zinc finger protein 419 1.437381 0.03921324 TRNT1 tRNA nucleotidyl transferase, CCA-adding, 1 1.436917 0.01566898 RNASEH2C ribonuclease H2, subunit C 1.436884 0.04326723 UBXN1 UBX domain protein 1 1.436743 0.01261269 AHCY adenosylhomocysteinase 1.436738 0.0251681 C Iorf5 1 chromosome 1 open reading frame 5 1 1.43641 0.0452643 DTL denticleless homolog (Drosophila) 1.436258 0.00228503 SPAG7 sperm associated antigen 7 1.435961 0.02176801 nuclear receptor subfamily 1, group H, NR1H4 member 4 1.43593 0.01391427 CLASP 1 cytoplasmic linker associated protein 1 1.435908 0.02537964 DDHD1 DDHD domain containing 1 1.435652 0.02093535 KIF1A kinesin family member 1A 1.435186 0.04232803 DFNB31 Deafness, autosomal recessive 3 1 1.434434 0.0130253 kinase non-catalytic C-lobe domain (KIND) KNDC1 containing 1 1.43423 0.04860364 SMOC1 SPARC related modular calcium binding 1 1.434133 0.01865818 roundabout homolog 4, magic roundabout ROB04 (Drosophila) 1.433999 0.0402941 WDR68 WD repeat domain 68 1.433988 0.01943028 KRT6B keratin 6B 1.433946 0.04035729 CTPS2 CTP synthase II 1.433712 0.00451117 Arginyl aminopeptidase (aminopeptidase B)- RNPEPL1 like 1 1.433653 0.0127466 RPL23A ribosomal protein L23a 1.433396 0.03929183 PI4KA phosphatidylinositol 4-kinase, catalytic, alpha 1.433153 0.01035201 ADRBK2 adrenergic, beta, receptor kinase 2 1.432822 0.03410394 LOC1001304 similar to P gene for c subunit of human 92 mitochondrial ATP synthase 1.432758 0.02573644 G-protein signaling modulator 1 (AGS3-like, GPSM1 C. elegans) 1.432471 0.01972055 SCRIB scribbled homolog (Drosophila) 1.431988 0.04023653 WFDC1 WAP four-disulfide core domain 1 1.431673 0.01610888 LMAN1L Lectin, mannose-binding, 1 like 1.431654 0.04178231 6-phosphofructo-2-kinase/fructose-2,6- PF FB3 biphosphatase 3 1.431618 0.04427076 gamma-aminobutyric acid (GABA) B GABBR2 receptor, 2 1.431377 0.01905578 TRM5 tRNA methyltransferase 5 homolog TRMT5 (S. cerevisiae) 1.431236 0.01264871 SYT15 synaptotagmin XV 1.431127 0.0468319 RBM6 RNA binding motif protein 6 1.43099 0.0074634 DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value complement component 4A (Rodgers blood C4A group) 1.430559 0.01 175462 ATP-binding cassette, sub-family B ABCB1 (MDR/TAP), member 1 1.430367 0.02609242 ZNF174 zinc finger protein 174 1.430263 0.02382622 ASAM adipocyte-specific adhesion molecule 1.429698 0.01575073 SULF2 sulfatase 2 1.429509 0.03707728 PCSK1 proprotein convertase subtilisin/kexin type 1 1.429504 0.00675947 DEXI Dexi homolog (mouse) 1.4295 0.00979015 CREB5 cAMP responsive element binding protein 5 1.429176 0.03559724 ITK IL2-inducible T-cell kinase 1.429076 0.04169545 PGAP1 post-GPI attachment to proteins 1 1.429043 0.02809428 cadherin, EGF LAG seven-pass G-type CELSR1 receptor 1 (flamingo homolog, Drosophila) 1.428928 0.01308152 FOXM1 forkhead box Ml 1.428823 0.00664337 sialic acid binding Ig-like lectin 1, SIGLECl sialoadhesin 1.428823 0.03063211 DTX2 deltex homolog 2 (Drosophila) 1.428784 0.01838192 PRRT1 proline-rich transmembrane protein 1 1.428698 0.00624586 C14orfl33 Chromosome 14 open reading frame 133 1.428084 0.01192022 GRM5 glutamate receptor, metabotropic 5 1.428 0.00569792 general transcription factor IIF, polypeptide 2, GTF2F2 30kDa 1.427729 0.03320271 XRRA1 X-ray radiation resistance associated 1 1.42764 0.02680118 sodium channel, voltage-gated, type V, alpha SCN5A subunit 1.427595 0.04117775 YST2 MYST histone acetyltransferase 2 1.427383 0.0315683 FZD5 frizzled homolog 5 (Drosophila) 1.427287 0.00237956 SYNE2 spectrin repeat containing, nuclear envelope 2 1.427261 0.02730996 ZNF787 zinc finger protein 787 1.427139 0.04991913 gamma-aminobutyric acid (GABA) A GABRD receptor, delta 1.426991 0.00917325 OPRLl opiate receptor-like 1 1.426883 0.00697309 FZD6 frizzled homolog 6 (Drosophila) 1.426781 0.02987967 KRTAP21-2 keratin associated protein 21-2 1.426314 0.01330069 TMEM63A transmembrane protein 63A 1.426248 0.02568617 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), LILRB1 member 1 1.425524 0.0481 1093 solute carrier family 24 (sodium/potassium/calcium exchanger), SLC24A6 member 6 1.425131 0.00428639 MY05B myosin VB 1.424893 0.04053217 UBE2Z ubiquitin-conjugating enzyme E2Z 1.424388 0.04566522 major facilitator superfamily domain MFSD3 containing 3 1.424253 0.03529744 ankyrin repeat, SAM and basic leucine zipper ASZ1 domain containing 1 1.423832 0.00549437 MORC3 MORC family CW-type zinc finger 3 1.423767 0.0282166 COQ6 coenzyme Q6 homolog, monooxygenase (S. 1.423745 0.01763509 DB1/ 69437 5 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value cerevisiae) ITGB4 integrin, beta 4 1.423742 0.00487711 SRP54 signal recognition particle 54kDa 1.423741 0.02741312 VPRBP Vpr (HIV-1) binding protein 1.423671 0.01590628 SCRN3 secernin 3 1.423637 0.00924737 TMEM196 transmembrane protein 1 6 1.423504 0.03912515 PAX4 paired box 4 1.4234 0.03546965 H3F3B H3 histone, family 3B (H3.3B) 1.423228 0.0202904 LYNX1 Ly6/neurotoxin 1 1.423037 0.0006764 IL21R interleukin 2 1 receptor 1.42299 0.0210596 VAC 14 Vac 14 homolog (S. cerevisiae) 1.422842 0.03352068 Purinergic receptor P2Y, G-protein coupled, P2RY12 12 1.42284 0.03032864 solute carrier family 39 (zinc transporter), SLC39A7 member 7 1.422776 0.00564315 RAB1 1FIP5 RAB1 1 family interacting protein 5 (class I) 1.422343 0.02262736 polyamine modulated factor 1 binding protein PMFBP1 1 1.422189 0.04357855 GPR1 15 G protein-coupled receptor 115 1.422028 0.03195424 RRAGB Ras-related GTP binding B 1.421971 0.04892957 MNX1 motor neuron and pancreas homeobox 1 1.421965 0.02578174 CCDC27 coiled-coil domain containing 27 1.421938 0.00474015 low density lipoprotein receptor-related LRP1B protein IB 1.421678 0.00833432 INPP5E inositol polyphosphate-5 -phosphatase, 72 kDa 1.421631 0.00536565 vacuolar protein sorting 53 homolog (S. VPS53 cerevisiae) 1.421566 0.04694093 TIMP4 TIMP metallopeptidase inhibitor 4 1.421302 0.00096167 procollagen-lysine 1, 2-oxoglutarate 5- PLOD1 dioxygenase 1 1.421203 0.03569493 DKFZp451A2 11 DKFZp451A211 protein 1.421088 0.04583309 C4orf29 chromosome 4 open reading frame 29 1.421085 0.03705249 pleckstrin homology domain containing, PLEKHB1 family B (evectins) member 1 1.420822 0.00910407 XAGEIA X antigen family, member 1A 1.420684 0.00468609 ring finger and CHY zinc finger domain RCHY1 containing 1 1.420477 0.00583725 FGL2 fibrinogen-like 2 1.419858 0.02205817 DOCK6 dedicator of cytokinesis 6 1.419724 0.00615545 GIGYF2 GRB10 interacting GYF protein 2 1.419681 0.04428945 degenerative spermatocyte homolog 1, lipid DEGS1 desaturase (Drosophila) 1.419499 0.017395 Bactericidal/permeability-increasing protein BPIL2 like 2 1.419455 0.02723426 LPHN3 latrophilin 3 1.419388 0.04837424 TMEM67 transmembrane protein 67 1.419169 0.04411419 ectonucleoside triphosphate ENTPD5 diphosphohydrolase 5 1.419164 0.02048402 CEP72 centrosomal protein 72kDa 1.419136 0.02292996 )B1/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value AMOTL1 angiomotin like 1 1.418766 0.01087323 ATPase, Ca++ transporting, plasma ATP2B2 membrane 2 1.418552 0.04957391 VGLL4 vestigial like 4 (Drosophila) 1.41834 0.04794193 solute carrier family 37 (glycerol-3-phosphate SLC37A3 transporter), member 3 1.41767 0.0252969 ZNF658 zinc finger protein 658 1.417326 0.01854368 FTSJD2 FtsJ methyltransferase domain containing 2 1.417106 0.04306268 ADIPOR1 adiponectin receptor 1 1.417013 0.02325571 ArfGAP with RhoGAP domain, ankyrin ARAP1 repeat and PH domain 1 1.41686 0.01952002 KDM4C lysine (K)-specific demethylase 4C 1.416713 0.01518097 MRPL48 mitochondrial ribosomal protein L48 1.416469 0.03672311 BOLA3 bolA homolog 3 (E. coli) 1.416326 0.04327928 VGF VGF nerve growth factor inducible 1.416295 0.01054276 NRAP nebulin-related anchoring protein 1.416244 0.03451808 ABHD1 1 abhydrolase domain containing 11 1.416205 0.04257664 cutA divalent cation tolerance homolog (E. CUTA coli) 1.41605 0.00410166 OTUB2 OTU domain, ubiquitin aldehyde binding 2 1.415713 0.0037679 rabaptin, RAB GTPase binding effector RABEP2 protein 2 1.415527 0.01931713 EXOC2 exocyst complex component 2 1.41514 0.00306119 C5orf44 chromosome 5 open reading frame 44 1.415138 0.00720595 ENGASE endo-beta-N-acetylglucosaminidase 1.414899 0.01551833 HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7 1.414871 0.02314324 family with sequence similarity 59, member FAM59A A 1.414685 0.01858809 ATP-binding cassette, sub-family A (ABCl), ABCA5 member 5 1.414504 0.01366697 ADPRHL1 ADP-ribosylhydrolase like 1 1.41442 0.04904569 TCEAL2 transcription elongation factor A (Sll)-like 2 1.414201 0.02452442 phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, PDE4D Drosophila) 1.414178 0.0113491 TUBE1 tubulin, epsilon 1 1.414105 0.00144696 MYOCD myocardin 1.414081 0.04496923 CKMT2 creatine kinase, mitochondrial 2 (sarcomeric) 1.414046 0.0128032 CYFIP2 cytoplasmic FMR1 interacting protein 2 1.413943 0.01863851 CUZD1 CUB and zona pellucida-like domains 1 1.413924 0.00851985 FM03 flavin containing monooxygenase 3 1.4139 0.02493988 ABLIM1 actin binding LIM protein 1 1.413544 0.04823307 tankyrase, TRF1 -interacting ankyrin-related TNKS2 ADP-ribose polymerase 2 1.413046 0.03105238 CPNE1 copine I 1.412965 0.00879491 BTBD7 BTB (POZ) domain containing 7 1.412938 0.0451493 protein phosphatase, EF-hand calcium PPEF2 binding domain 2 1.412887 0.01372869 TMEM45B transmembrane protein 45B 1.412854 0.02498117 NECAB2 N-terminal EF-hand calcium binding protein 1.412734 0.00482513 B l / 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value 2 signal-induced proliferation-associated 1 like SIPA1L1 1 1.412649 0.03131075 TTC13 tetratricopeptide repeat domain 3 1.412549 0.02575639 epithelial cell transforming sequence 2 ECT2 oncogene 1.412257 0.00609004 mitogen-activated protein kinase kinase MAP3K5 kinase 5 1.412219 0.0127853 IL17RC interleukin 17 receptor C 1.412013 0.01 14419 ectonucleotide ENPP6 pyrophosphatase/phosphodiesterase 6 1.411987 0.02580456 menage a trois homolog 1, cyclin H assembly M AT 1 factor (Xenopus laevis) 1.411922 0.02407525 CLCA3P chloride channel accessory 3 (pseudogene) 1.411853 0.04263647 calcium channel, voltage-dependent, beta 2 CACNB2 subunit 1.41 1807 0.0276152 CASC5 cancer susceptibility candidate 5 1.411558 0.00946303 HK1 hexokinase 1 1.41 114 0.04448314 CALR calreticulin 1.41 1 0.04006515 C8orf38 chromosome 8 open reading frame 38 1.410974 0.02540992 FLJ45950 FLJ45950 protein 1.410895 0.03436742 inositol polyphosphate-4-phosphatase, type II, I PP4B 105kDa 1.41084 0.03007155 C5orf24 chromosome 5 open reading frame 24 1.41066 0.02510297 LY6H lymphocyte antigen 6 complex, locus H 1.410606 0.0133544 PTH1R parathyroid hormone 1 receptor 1.410543 0.00783519 intraflagellar transport 57 homolog IFT57 (Chlamydomonas) 1.410484 0.02169174 DY C1 2 dynein, cytoplasmic 1, intermediate chain 2 1.410334 0.0279939 pregnancy specific beta- -glycoprotein 7 PSG7 (gene/pseudogene) 1.410282 0.03956582 FGFRL1 fibroblast growth factor receptor-like 1 1.410036 0.04769822 DAO D-amino-acid oxidase 1.409682 0.01256402 SULF1 sulfatase 1 1.409417 0.02525754 protein phosphatase 2, regulatory subunit B', PPP2R5D delta 1.409369 0.02720365 ECHDC2 enoyl CoA hydratase domain containing 2 1.409332 0.0282362 cylicin, basic protein of sperm head CYLC2 cytoskeleton 2 1.409008 0.03520158 C3orf20 chromosome 3 open reading frame 20 1.408985 0.01768384 TKTL1 transketolase-like 1 1.408946 0.01008055 C5orf26 Chromosome 5 open reading frame 26 1.408597 0.00536435 FNDC4 fibronectin type III domain containing 4 1.408025 0.02248347 superkiller viralicidic activity 2-like (S. SKIV2L cerevisiae) 1.407726 0.00726796 DVL1 dishevelled, dsh homolog 1 (Drosophila) 1.407381 0.01421061 SRD5A3 steroid 5 alpha-reductase 3 1.407294 0.04982272 GPR98 G protein-coupled receptor 98 1.407268 0.01027858 NLGN1 neuroligin 1 1.407195 0.01 186509 UQCRC1 ubiquinol-cytochrome c reductase core 1.407184 0.01608345 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value protein I OSBPL9 Oxysterol binding protein-like 9 1.406858 0.02191 181 UBTD2 ubiquitin domain containing 2 1.406757 0.02310731 TARSL2 threonyl-tRNA synthetase-like 2 1.406743 0.03616151 DPF2 D4, zinc and double PHD fingers family 2 1.406662 0.00964088 asparagine-linked glycosylation 9, alpha- 1,2- ALG9 mannosyltransferase homolog (S. cerevisiae) 1.406114 0.02876208 MXD4 MAX dimerization protein 4 1.406008 0.0335339 ZNF517 zinc finger protein 517 1.405979 0.0127863 C13orf31 chromosome 13 open reading frame 31 1.405851 0.02596859 JTV1 JTV1 gene 1.405782 0.00950045 SASH1 SAM and SH3 domain containing 1 1.404986 0.01632024 solute carrier family 6 (neurotransmitter SLC6A8 transporter, creatine), member 8 1.404866 0.03216539 H2AFV H2A histone family, member V 1.40403 0.03700618 CUL7 cullin 7 1.403988 0.01660501 ST7 suppression of tumorigenicity 7 1.403839 0.01748328 RP1L1 retinitis pigmentosa 1-like 1 1.40353 0.03560601 La ribonucleoprotein domain family, member LARP4 4 1.403388 0.02344304 sodium channel, voltage-gated, type IV, alpha SCN4A subunit 1.402997 0.00767131 DOK6 docking protein 6 1.402978 0.04549792 nucleolar complex associated 3 homolog (S. NOC3L cerevisiae) 1.402952 0.0370841 1 NECAP2 NECAP endocytosis associated 2 1.402829 0.032084 LMCD1 L M and cysteine-rich domains 1 1.402766 0.03712631 N-deacetylase/N-sulfotransferase (heparan NDST1 glucosaminyl) 1 1.402735 0.03263743 TBCKL N/A 1.402699 0.03188772 ZNF770 zinc finger protein 770 1.402633 0.00386837 IAA 1797 KIAA1797 1.402343 0.00803293 CENPC1 centromere protein C 1 1.402049 0.0016592 WEE1 WEE1 homolog (S. pombe) 1.401628 0.01546795 GLT25D1 glycosyltransferase 25 domain containing 1 1.401591 0.0059023 COL1A2 collagen, type I, alpha 2 1.401494 0.03357532 SH3BP5L SH3 -binding domain protein 5-like 1.401407 0.0460964 GRRPl glycine/arginine rich protein 1 1.400911 0.02169507 FBXL18 F-box and leucine-rich repeat protein 8 1.400868 0.03213365 TMEM5 transmembrane protein 5 1.400644 0.02448413 PRKCD protein kinase C, delta 1.400535 0.00850696 MEIS1 Meis homeobox 1 1.400454 0.04054264 nuclear factor of kappa light polypeptide gene NFKBIL1 enhancer in B-cells inhibitor-like 1 1.400366 0.02647057 SLC35A5 solute carrier family 35, member A5 1.400233 0.00237093 solute carrier family 36 (proton/amino acid SLC36A1 symporter), member 1 1.399675 0.02076631 ANXA2P1 annexin A2 pseudogene 1 1.399533 0.02940857 ANKRD5 ankyrin repeat domain 5 1.399432 0.0007459 PARVG parvin, gamma 1.399324 0.00164838 DB1/ 6943751 6 . 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value mitogen-activated protein kinase kinase MAP4K5 kinase kinase 5 1.399107 0.02479176 ZNF100 Zinc finger protein 100 1.398985 0.00625826 CATSPER2 cation channel, sperm associated 2 1.398976 0.00496629 C6orfl05 chromosome 6 open reading frame 05 1.398805 0.04529836 serum/glucocorticoid regulated kinase family, SG 3 member 3 1.398376 0.04615825 Protein tyrosine phosphatase, non-receptor PTPN5 type 5 (striatum-enriched) 1.398369 0.00577337 TNKS1BP1 tankyrase 1 binding protein 1, 182kDa 1.398288 0.00506839 DENND5A DENN/MADD domain containing 5A 1.398194 0.0134378 SMAD5 SMAD family member 5 1.397969 0.041 12916 GPR85 G protein-coupled receptor 85 1.397847 0.01995992 retinol dehydrogenase 11 (all-trans/9-cis/l 1- RDH1 1 cis) 1.397657 0.0050891 ZNF92 Zinc finger protein 92 1.397295 0.01910671 C6orfl23 Chromosome 6 open reading frame 123 1.397278 0.01660509 TULP4 tubby like protein 4 1.397015 0.02174879 GAS2L2 growth arrest-specific 2 like 2 1.396857 0.00769112 MON2 MON2 homolog (S. cerevisiae) 1.396562 0.02277165 NCKAP1L NCK-associated protein 1-like 1.396475 0.03478304 RAB28 RAB28, member RAS oncogene family 1.396447 0.02485702 WASH2P WAS protein family homolog 2 pseudogene 1.396235 0.01601012 C2orf43 chromosome 2 open reading frame 43 1.396214 0.03663188 ZFHX4 zinc finger homeobox 4 1.395673 0.03745583 killer cell immunoglobulin-like receptor, two KIR2DL4 domains, long cytoplasmic tail, 4 1.395657 0.03599348 IKZF2 IKAROS family zinc finger 2 (Helios) 1.395479 0.03064697 Olfactory receptor, family 2, subfamily H, OR2H2 member 2 1.395417 0.04713191 olfactory receptor, family 2, subfamily B, OR2B2 member 2 1.395263 0.00597808 PTN kaptin (actin binding protein) 1.395175 0.00347347 LOC1001343 96 similar to zinc finger protein 799 1.39516 0.04812719 CDH2 cadherin 2, type 1, N-cadherin (neuronal) 1.395061 0.04529743 translocase of inner mitochondrial membrane TIMM44 44 homolog (yeast) 1.394702 0.02292879 ATP-binding cassette, sub-family F (GCN20), ABCF2 member 2 1.394627 0.03672061 ZNF193 zinc finger protein 193 1.393586 0.00256927 MOSPD2 motile sperm domain containing 2 1.393409 0.00750667 AMELX amelogenin, X-linked 1.393182 0.01706607 C20orfl49 Chromosome 20 open reading frame 149 1.392992 0.03940517 BLM Bloom syndrome, RecQ helicase-like 1.392962 0.02331052 PRMT8 protein arginine methyltransferase 8 1.392528 0.04848671 FOXP1 forkhead box P I 1.392398 0.03455442 ATP-binding cassette, sub-family G ABCG4 (WHITE), member 4 1.392177 0.02679048 ST13 suppression of tumorigenicity 13 (colon 1.392146 0.02567641 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value carcinoma) (Hsp70 interacting protein) GTF2A1L general transcription factor IIA, 1-like 1.392143 0.0445689 Clorf25 chromosome 1 open reading frame 25 1.391853 0.00399888 BBS2 Bardet-Biedl syndrome 2 1.391766 0.0482488 solute carrier family 34 (sodium phosphate), SLC34A2 member 2 1.391721 0.00394565 PPIA peptidylprolyl isomerase A (cyclophilin A) 1.391479 0.001351 16 secreted protein, acidic, cysteine-rich SPARC (osteonectin) 1.391088 0.04346937 LIMD1 LIM domains containing 1 1.390887 0.01945038 BAG2 BCL2-associated athanogene 2 1.390864 0.00399346 CNDP dipeptidase 2 (metallopeptidase M20 CNDP2 family) 1.39074 0.04661699 SGK2 serum/glucocorticoid regulated kinase 2 1.39068 0.03191632 PDE3A phosphodiesterase 3A, cGMP -inhibited 1.390545 0.04174219 FNDC7 fibronectin type III domain containing 7 1.390462 0.0021826 FLNC filamin C, gamma 1.390381 0.00718939 alcohol dehydrogenase 4 (class II), pi ADH4 polypeptide 1.390243 0.02064603 C6orfl0 chromosome 6 open reading frame 10 1.389954 0.0360883 ST6 beta-galactosamide alpha-2,6- ST6GAL1 sialyltranferase 1 1.389745 0.0351361 1 HELQ helicase, POLQ-like 1.389705 0.03292837 GGCX gamma-glutamyl carboxylase 1.38939 0.0460239 PI15 peptidase inhibitor 15 1.389099 0.02507614 nuclear receptor subfamily 1, group I, NR1I2 member 2 1.388937 0.00647909 PGPEP1 Pyroglutamyl-peptidase I 1.388913 0.00818542 family with sequence similarity 174, member FAM174B B 1.388897 0.0283348 PYCARD PYD and CARD domain containing 1.388828 0.02722781 SLC38A4 solute carrier family 38, member 4 1.38881 1 0.04897691 CENPP centromere protein P 1.388721 0.02320842 FCRL5 Fc receptor-like 5 1.388699 0.01992709 TM7SF3 transmembrane 7 superfamily member 3 1.388536 0.01990459 SLPI secretory leukocyte peptidase inhibitor 1.38852 0.04288421 SORT1 sortilin 1 1.388421 0.00563762 SIPA1 signal-induced proliferation-associated 1 1.388256 0.00350995 RAD52 RAD52 homolog (S. cerevisiae) 1.388195 0.01704318 sodium channel, voltage-gated, type III, alpha SCN3A subunit 1.387952 0.03410646 Cllorfl6 chromosome 11 open reading frame 16 1.387896 0.01527868 KDELC2 KDEL (Lys-Asp-Glu-Leu) containing 2 1.387517 0.03464133 SYTL4 synaptotagmin-like 4 1.3871 18 0.02970297 POTEA POTE ankyrin domain family, member A 1.387003 0.04607794 C4orf8 Chromosome 4 open reading frame 8 1.386989 0.03542979 LTA4H leukotriene A4 hydrolase 1.386545 0.03548382 C14orfl77 chromosome 14 open reading frame 177 1.386309 0.00984611 GBP4 guanylate binding protein 4 1.386077 0.04580035 RRP9 ribosomal RNA processing 9, small subunit 1.386013 0.00671923 DB1/ 6943751 6 . 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value (SSU) processome component, homolog (yeast) SIK2 salt-inducible kinase 2 0.04197294 NKD1 naked cuticle homolog 1 (Drosophila) 0.03408552 UBE3B ubiquitin protein ligase E3B 0.04875568 YR1 ryanodine receptor 1 (skeletal) 0.02386302 MAK male germ cell-associated kinase 0.04875467 Ras protein-specific guanine nucleotide- RASGRF1 releasing factor 1 0.04400616 ULK3 unc-51-like kinase 3 (C. elegans) 0.04520021 NKTR natural killer-tumor recognition sequence 0.03433816 C5orf51 chromosome 5 open reading frame 5 1 0.01685538 MYCBP2 MYC binding protein 2 0.0259911 1 MEX3B mex-3 homolog B (C. elegans) 0.01461286 family with sequence similarity 50, member FAM50A A 0.02964922 NVL nuclear VCP-like 0.02522613 CD96 CD96 molecule 0.00301321 CllorGO chromosome 11 open reading frame 30 0.01287423 ST6 (alpha-N-acetyl-neuraminyl-2,3 -beta- ST6GALNAC galactosyl-l,3)-N-acetylgalactosaminide 3 alpha-2,6-sialyltransferase 3 0.01459722 CD99L2 CD99 molecule-like 2 0.02914173 ALAD aminolevulinate dehydratase 0.0424931 1 FL Friend leukemia virus integration 1 0.04745503 kelch repeat and BTB (POZ) domain BTBD2 containing 2 0.02264339 myosin, light chain 12A, regulatory, non- MYL12A sarcomeric 0.01246539 v-erb-a erythroblastic leukemia viral ERBB4 oncogene homolog 4 (avian) 0.02315776 KPNA3 karyopherin alpha 3 (importin alpha 4) 0.0289694 WW domain binding protein 4 (formin WBP4 binding protein 21) 0.04909614 KIF13B kinesin family member 13B 0.04347903 SPOCD1 SPOC domain containing 1 0.02601498 sarcoglycan, alpha (50kDa dystrophin- SGCA associated glycoprotein) 0.00441295 SNX19 Sorting nexin 19 0.03833771 solute carrier family 12 (potassium/chloride SLC12A6 transporters), member 6 0.02817791 CAMTA1 calmodulin binding transcription activator 1 0.04779083 EFHD2 EF-hand domain family, member D2 0.01067716 MDM4 Mdm4 p53 binding protein homolog (mouse) 0.04659048 amyloid beta (A4) precursor protein-binding, APBB3 family B, member 3 0.03664956 GPR135 G protein-coupled receptor 135 0.04040497 mitochondrial rRNA methyltransferase 1 MRM1 homolog (S. cerevisiae) 0.0007521 HTRA2 HtrA serine peptidase 2 0.04940812 DB1/ 69437 5 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value KIRREL3 kin of IRRE like 3 (Drosophila) 1.381017 0.00737628 syntrophin, beta 2 (dystrophin-associated SNTB2 protein Al, 59kDa, basic component 2) 1.380994 0.02123007 M S1 Meckel syndrome, type 1 1.380991 0.04213353 HERC6 hect domain and RLD 6 1.380985 0.01442056 CPLX2 complexin 2 1.380866 0.04521856 IP6K3 inositol hexakisphosphate kinase 3 1.38025 0.00952223 PDZRN3 PDZ domain containing ring finger 3 1.380245 0.00918114 AQP6 aquaporin 6, kidney specific 1.379963 0.03940188 USP8 ubiquitin specific peptidase 8 1.379749 0.01506322 CCDC93 coiled-coil domain containing 93 1.379414 0.03060352 leukocyte immunoglobulin-like receptor, LILRA3 subfamily A (without TM domain), member 3 1.37924 0.04854274 PI-3-kinase-related kinase SMG-1 LOC595101 pseudogene 1.3791 13 0.03181381 FGFR4 fibroblast growth factor receptor 4 1.379071 0.02539936 ZNF16 zinc finger protein 16 1.37864 0.02760601 MTSS1 metastasis suppressor 1 1.378356 0.01047276 RNFT2 ring finger protein, transmembrane 2 1.37832 0.01084488 PIPSL PIP5K1 A and PSMD4-like 1.37826 0.03426384 ZNF597 zinc finger protein 597 1.378182 0.01974716 PH domain and leucine rich repeat protein PHLPP phosphatase 1.378024 0.03544604 nuclear factor related to kappaB binding NFRKB protein 1.377916 0.00803175 UTP6, small subunit (SSU) processome UTP6 component, homolog (yeast) 1.377461 0.04338852 GIMAP5 GTPase, IMAP family member 5 1.377391 0.00262894 ribosomal protein S6 kinase, 90kDa, RPS6KA2 polypeptide 2 1.377333 0.03489272 PRKCB protein kinase C, beta 1.377304 0.0430421 zinc finger, RAN-binding domain containing ZRANB3 3 1.377256 0.02630989 GPR133 G protein-coupled receptor 133 1.377234 0.02937482 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX60 60 1.377194 0.01933972 UDP-N-acetyl-alpha-D- galactosamine.polypeptide N- acetylgalactosaminyltransferase 11 (GalNAc- GALNT11 Tll) 1.37695 0.04489588 FOXD1 forkhead box D l 1.376873 0.00527696 PTDSS1 phosphatidylserine synthase 1 1.376364 0.01628131 COL12A1 collagen, type XII, alpha 1 1.376147 0.04737272 CALB1 calbindin 1, 28kDa 1.37604 0.02319277 F9 coagulation factor IX 1.375946 0.04016998 TNXA tenascin XA pseudogene 1.375903 0.0271 1531 CD8A CD8a molecule 1.375754 0.01878319 NGFI-A binding protein 1 (EGR1 binding NAB1 protein 1) 1.375422 0.02338057 FERMT3 fermitin family homolog 3 (Drosophila) 1.375379 0.03007465 ) 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ZNF394 Zinc finger protein 394 1.375341 0.0292037 DNAH10 Dynein, axonemal, heavy chain 10 1.375307 0.02636417 USP38 ubiquitin specific peptidase 38 1.37522 0.04727816 PH G1 phosphorylase kinase, gamma 1 (muscle) 1.37485 0.03284559 YY1AP1 YY1 associated protein 1 1.374742 0.02095981 inositol polyphosphate-5 -phosphatase, I PP5D 145kDa 1.374524 0.00364048 CLSTN2 calsyntenin 2 1.374429 0.00355959 ECM1 extracellular matrix protein 1 1.374408 0.0430531 USP25 ubiquitin specific peptidase 25 1.374384 0.01432184 CHKA choline kinase alpha 1.374342 0.02812555 Rho guanine nucleotide exchange factor ARHGEF10L (GEF) 10-like 1.374329 0.04034993 WDR6 WD repeat domain 6 1.374259 0.04345138 TFCP2 transcription factor CP2 1.373815 0.0381982 PMS2L11 N/A 1.373707 0.01103585 KDELC1 KDEL (Lys-Asp-Glu-Leu) containing 1 1.37365 0.0092781 MEDIO mediator complex subunit 0 1.373572 0.01287145 family with sequence similarity 135, member FAM135A A 1.373455 0.03341903 BCL2L1 BCL2-like 1 1.373446 0.02246357 ADAM metallopeptidase with ADAMTS2 thrombospondin type 1 motif, 2 1.373402 0.03624825 CLCN7 chloride channel 7 1.373344 0.03694279 C3orf23 chromosome 3 open reading frame 23 1.373321 0.03609232 phospholipase Dl, phosphatidylcholine- PLD1 specific 1.373202 0.04783635 cytidine monophosphate (UMP-CMP) kinase CMPK2 2, mitochondrial 1.373034 0.04652844 membrane protein, palmitoylated 5 (MAGUK MPP5 p55 subfamily member 5) 1.372794 0.01412992 C21orf67 chromosome open reading frame 67 1.372758 0.03063945 H0XC8 homeobox C8 1.372535 0.03904603 PSTK phosphoseryl-tRNA kinase 1.372512 0.0045338 TM2D1 TM2 domain containing 1 1.372504 0.03854133 Amyotrophic lateral sclerosis 2 (juvenile) ALS2CR8 chromosome region, candidate 8 1.372445 0.006561 caspase 6, apoptosis-related cysteine CASP6 peptidase 1.372269 0.04203738 MGC16385 Hypothetical protein MGC 16385 1.372209 0.03824835 SFRS17A splicing factor, arginine/serine-rich 17A 1.371645 0.04315668 RXRG retinoid X receptor, gamma 1.371558 0.01357285 ACACB acetyl-CoA carboxylase beta 1.371543 0.01865922 KIAA1310 KIAA1310 1.371445 0.03626434 VEGFA vascular endothelial growth factor A 1.371401 0.00112732 Family with sequence similarity 74, member FAM74A3 A3 1.371 195 0.04290608 Neural precursor cell expressed, NEDD1 developmentally down-regulated 1 1.371 19 0.0359751 OR2T3 Olfactory receptor, family 2, subfamily T, 1.371188 0.0318152 DBI/69437516. I Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value member 3 solute carrier family 16, member 0 (aromatic SLC16A10 amino acid transporter) 1.371 154 0.02266337 vacuolar protein sorting 24 homolog (S. VPS24 cerevisiae) 1.371119 0.04148419 CD44 CD44 molecule (Indian blood group) 1.370793 0.00355826 TAT tyrosine aminotransferase 1.370675 0.01325271 CLCNKA chloride channel Ka 1.370649 0.00486945 NOTCH2 Notch homolog 2 (Drosophila) 1.370623 0.0341 1534 solute carrier family 5 (sodium/glucose SLC5A10 cotransporter), member 10 1.37042 0.04271008 purinergic receptor P2Y, G-protein coupled, P2 Y13 13 1.370289 0.00291615 NCAPH non-SMC condensin I complex, subunit H 1.370164 0.01932908 PRSS22 protease, serine, 22 1.370127 0.04061674 TMEM87B transmembrane protein 8 B 1.369897 0.0223541 PTPRH protein tyrosine phosphatase, receptor type, H 1.369696 0.031 19341 janus kinase and microtubule interacting JAKMIP1 protein 1 1.369683 0.01769588 intrafiagellar transport 74 homolog IFT74 (Chlamydomonas) 1.369324 0.01094548 TBC1D4 TBC1 domain family, member 4 1.369181 5.58E-05 NUP210L nucleoporin 210kDa-like 1.369063 0.02464659 Olfactory receptor, family 6, subfamily W, OR6W1P member 1 pseudogene 1.369057 0.04445932 SNAP29 synaptosomal-associated protein, 29kDa 1.368977 0.04802207 Golgi autoantigen, golgin subfamily a, 2-like, GOLGA2LY1 Y-linked 1 1.368455 0.00642459 CDC 14 cell division cycle 4 homolog B (S. CDC14B cerevisiae) 1.368453 0.04864209 TRIM45 tripartite motif-containing 45 1.36841 0.02057028 Cl lorf2 chromosome 11 open reading frame 2 1.368238 0.04591 136 MERTK c-mer proto-oncogene tyrosine kinase 1.368201 0.01656551 Basic, immunoglobulin-like variable motif BIVM containing 1.36808 0.02640504 NADPH oxidase, EF-hand calcium binding NOX5 domain 5 1.367954 0.04018162 MEF2B myocyte enhancer factor 2B 1.367631 0.03665346 ANGPTL4 Angiopoietin-like 4 1.36763 0.03038604 RGS22 regulator of G-protein signaling 22 1.367621 0.01221356 CT BL1 catenin, beta like 1 1.367091 0.01718999 neutral sphingomyelinase (N-SMase) NSMAF activation associated factor 1.367032 0.03987999 HAMP hepcidin antimicrobial peptide 1.366953 0.01646212 PRDX6 peroxiredoxin 6 1.366944 0.04515275 ATP-binding cassette, sub-family A (ABC1), ABCA1 member 1 1.366742 0.00856212 TTL tubulin tyrosine ligase 1.366725 0.02531198 C4orf41 chromosome 4 open reading frame 4 1 1.366403 0.01849862 C17orf63 chromosome 17 open reading frame 63 1.366389 0.03570733 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SOX13 SPvY (sex determining region Y)-box 13 1.36636 0.01564496 pre-B-cell leukemia homeobox interacting PBXIP1 protein 1 1.366227 0.00453036 TCTN1 tectonic family member 1 1.366123 0.010648 PRKD1 protein kinase D l 1.366096 0.02015636 NFE2L1 nuclear factor (erythroid-derived 2)-like 1 1.366058 0.00030326 GRB2 -binding adaptor protein, GAPT transmembrane 1.366056 0.00139747 TNF tumor necrosis factor 1.365785 0.01449054 IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745 PTPRD protein tyrosine phosphatase, receptor type, D 1.365298 0.02363435 ZZZ3 zinc finger, ZZ-type containing 3 1.36524 0.02901362 ODF1 outer dense fiber of sperm tails 1 1.365172 0.02776627 NTRK2 neurotrophic tyrosine kinase, receptor, type 2 1.365093 0.02245205 KIAA0195 KIAA0195 1.365032 0.02929526 DUSP5P dual specificity phosphatase 5 pseudogene 1.364973 0.04615392 POLR1D polymerase (RNA) I polypeptide D, 16kDa 1.364918 0.02725572 ENPEP glutamyl aminopeptidase (aminopeptidase A) 1.364897 0.0451536 adenylate cyclase activating polypeptide 1 ADCYAPIRI (pituitary) receptor type I 1.364667 0.0398011 FAM65B family with sequence similarity 65, member B 1.364604 0.02320728 CENPK centromere protein K 1.364588 0.03575031 MTERFD2 MTERF domain containing 2 1.36445 0.01687718 ATP8B2 ATPase, class I, type 8B, member 2 1.364282 0.01260885 pleckstrin homology domain containing, PLEKHH2 family H (with MyTH4 domain) member 2 1.364214 0.02614524 NFU1 iron-sulfur cluster scaffold homolog NFU1 (S. cerevisiae) 1.364152 0.02126921 Rho/Rac guanine nucleotide exchange factor ARHGEF2 (GEF) 2 1.364141 0.0009248 METTL3 methyltransferase like 3 1.364042 0.00405217 NGFI-A binding protein 2 (EGR1 binding NAB2 protein 2) 1.364006 0.02567161 bile acid CoA: amino acid N-acyltransferase BAAT (glycine N-choloyltransferase) 1.363683 0.02579747 WDR44 WD repeat domain 44 1.363614 0.02783348 UDP-GlcNAc:betaGal beta-l,3-N- B3GNTL1 acetylglucosaminyltransferase-like 1 1.363544 0.00190917 EMILIN3 elastin microfibril interfacer 3 1.363472 0.00980223 C15orf40 chromosome 15 open reading frame 40 1.363453 0.04965862 methylenetetrahydrofolate dehydrogenase MTHFD1L (NADP+ dependent) 1-like 1.363389 0.00547608 TDRD5 tudor domain containing 5 1.363085 0.02402684 PCDHB5 protocadherin beta 5 1.363007 0.01410305 cytochrome P450, family 2, subfamily A, CYP2A7 polypeptide 7 1.36287 0.03869986 polymerase (RNA) II (DNA directed) POLR2C polypeptide C, 33kDa 1.362858 0.04997226 adenosine deaminase, RNA-specific, B2 ADARB2 (RED2 homolog rat) 1.362617 0.02314728 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value solute carrier family 11 (proton-coupled SLC11A2 divalent metal ion transporters), member 2 1.362551 0.00212935 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing RCBTB2 protein 2 1.362522 0.0387415 SUSD4 sushi domain containing 4 1.362469 0.04400647 NPC1 Niemann-Pick disease, type CI 1.362315 0.04477366 ADAMDEC1 ADAM-like, decysin 1 1.362129 0.03679769 GMPPA GDP-mannose pyrophosphorylase A 1.362062 0.03362215 MYO10 myosin X 1.361879 0.04208556 DOCK1 dedicator of cytokinesis 1 1.361725 0.006188 ASB16 ankyrin repeat and SOCS box-containing 16 1.361515 0.02673649 leucine rich repeat and fibronectin type III LRFN5 domain containing 5 1.361441 0.00683786 SCOC short coiled-coil protein 1.361401 0.02982515 FLJ43950 FAM75-like protein FLJ46321 pseudogene 1.36124 0.03910104 PRKCZ protein kinase C, zeta 1.360589 0.0125831 BRPF1 bromodomain and PHD finger containing, 1 1.360487 0.03928809 PTPRJ protein tyrosine phosphatase, receptor type, J 1.360438 0.03523859 tumor necrosis factor (ligand) superfamily, TNFSF1 1 member 1 1.360371 0.01940588 FZD3 frizzled homolog 3 (Drosophila) 1.36018 0.03737165 PITX3 paired-like homeodomain 3 1.360032 0.03254832 ZCCHC2 zinc finger, CCHC domain containing 2 1.359997 0.03782226 Pantothenate kinase 2 (Hallervorden-Spatz PANK2 syndrome) 1.359972 0.01813668 UDP-N-acteylglucosamine UAP1 pyrophosphorylase 1 1.359785 0.01606561 C8orf37 chromosome 8 open reading frame 37 1.359433 0.01568876 ESR2 estrogen receptor 2 (ER beta) 1.359245 0.02848424 DEAH (Asp-Glu-Ala-His) box polypeptide DHX38 38 1.359196 0.04968719 ZXDC ZXD family zinc finger C 1.359056 0.044341 11 TATA box binding protein (TBP)-associated TAF1B factor, RNA polymerase I, B, 63kDa 1.35891 0.00465628 COL11A1 collagen, type XI, alpha 1 1.358775 0.01500244 leucine-rich repeat-containing G protein- LGR4 coupled receptor 4 1.358736 0.02256386 VIL1 villin 1 1.358667 0.03021292 GLIS2 GLIS family zinc finger 2 1.358655 0.02208258 IL1R2 Interleukin 1 receptor, type II 1.358531 0.04399534 CKB creatine kinase, brain 1.358461 0.01419595 Rtfl, Pafl/RNA polymerase II complex RTF1 component, homolog (S. cerevisiae) 1.358008 0.00507983 solute carrier family 34 (sodium phosphate), SLC34A1 member 1 1.357953 0.01540008 RLF rearranged L-myc fusion 1.357779 0.00608573 dual-specificity tyrosine-(Y)-phosphorylation DYRK4 regulated kinase 4 1.357452 0.01059005 SLC30A8 solute carrier family 30 (zinc transporter), 1.357366 0.04578163 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value member 8 poliovirus receptor-related 1 (herpesvirus PVRL1 entry mediator C) 0.01512735 HFE hemochromatosis 0.03804853 3'-phosphoadenosine 5'-phosphosulfate PAPSS2 synthase 2 0.01527324 USP5 ubiquitin specific peptidase 5 (isopeptidase T) 0.02266555 PDLIM5 PDZ and LIM domain 5 0.03327639 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX25 25 0.00745677 CDH18 cadherin 18, type 2 0.01178932 ER degradation enhancer, mannosidase alpha¬ EDEM3 like 3 1.356732 0.04196012 CD59 molecule, complement regulatory CD59 protein 0.00238596 LLGL1 lethal giant larvae homolog 1 (Drosophila) 0.03396635 HARS histidyl-tRNA synthetase 0.03079558 GPR11 G protein-coupled receptor 111 0.01129072 solute carrier family 28 (sodium-coupled SLC28A3 nucleoside transporter), member 3 0.01558433 SC65 synaptonemal complex protein SC65 0.0041 156 ZNF544 zinc fmger protein 544 0.03669101 TNNT3 troponin T type 3 (skeletal, fast) 0.01223845 ZNF236 zinc finger protein 236 0.00612352 KIAA0664 KIAA0664 0.00939652 integrin-linked kinase-associated ILKAP serine/threonine phosphatase 2C 1.35462 0.00485523 fibroblast growth factor 3 (murine mammary tumor virus integration site (v-int-2) oncogene FGF3 homolog) 0.04298606 PELI1 pellino homolog 1 (Drosophila) 0.01691951 ZNHIT2 zinc finger, HIT type 2 0.04183563 SIRPB1 signal-regulatory protein beta 1 0.01437671 leucine-rich repeats and calponin homology LRCH1 (CH) domain containing 1 0.00280028 aryl-hydrocarbon receptor nuclear ARNT2 translocator 2 0.00923458 ATP-binding cassette, sub-family C ABCC2 (CFTR/MRP), member 2 0.01324965 ADAM23 ADAM metallopeptidase domain 23 0.00519005 NLRC5 NLR family, CARD domain containing 5 0.0138878 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- GALNTL2 acetylgalactosaminyltransferase-like 2 0.03969585 CIDEC cell death-inducing DFFA-like effector c 0.01386864 solute carrier family 9 (sodium/hydrogen SLC9A7 exchanger), member 7 1.352213 0.03119589 family with sequence similarity 87, member FAM87A A 0.02843837 MME membrane metallo-endopeptidase 0.04281673 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value PPIL2 peptidylprolyl isomerase (cyclophiiin)-like 2 0.03170762 FBXL4 F-box and leucine-rich repeat protein 4 0.00412396 carcinoembryonic antigen-related cell CEACAM20 adhesion molecule 20 1.35193 0.01783611 serum response factor (c-fos serum response S F element-binding transcription factor) 0.02938074 PIP prolactin-induced protein 0.02836164 ANKRD30A ankyrin repeat domain 3OA 0.03178457 SNCAIP synuclein, alpha interacting protein 0.00842294 GTPBP1 GTP binding protein 1 0.01449782 growth factor independent IB transcription GFI1B repressor 0.04386037 ATM ataxia telangiectasia mutated 0.02307203 LYST lysosomal trafficking regulator 0.00716237 OXTR oxytocin receptor 0.02047591 ATP synthase, H+ transporting, mitochondrial ATP5L2 F0 complex, subunit G2 0.02899822 DEN D3 DENN/MADD domain containing 3 0.00428396 nucleolar complex associated 2 homolog (S. NOC2L cerevisiae) 1.350431 0.04666038 synaptonemal complex central element SYCE1 protein 1 0.04034105 KIAA0415 KIAA0415 0.04599724 CXXC1 CXXC finger 1 (PHD domain) 0.03108404 NUAK1 NUAK family, SNFl-like kinase, 1 0.047671 12 v-maf musculoaponeurotic fibrosarcoma MAF oncogene homolog (avian) 1.349925 0.03533849 ADAM metallopeptidase with ADAMTS10 thrombospondin type 1 motif, 10 0.00906533 KLF5 Kruppel-like factor 5 (intestinal) 0.03913202 PAPD4 PAP associated domain containing 4 0.01316031 RGS17 regulator of G-protein signaling 1 0.03025957 KCNIP2 Kv channel interacting protein 2 0.02853969 RASAL2 RAS protein activator like 2 0.0405611 1 CNRIP1 cannabinoid receptor interacting protein 1 0.0092194 TARBP2 TAR (HIV-1) RNA binding protein 2 0.0213518 AVL9 AVL9 homolog (S. cerevisiase) 0.03542439 sema domain, immunoglobulin domain (Ig), SEMA3B short basic domain, secreted, (semaphorin) 3B 0.0227655 ZNF451 zinc finger protein 4 1 0.04749371 MIP major intrinsic protein of lens fiber 0.00400498 DNAI1 dynein, axonemal, intermediate chain 1 0.01203404 SLC38A5 solute carrier family 38, member 5 0.04248543 ZFYVE26 zinc finger, FYVE domain containing 26 0.04363 ODF2L outer dense fiber of sperm tails 2-like 0.01729239 ITPR2 inositol 1,4,5-triphosphate receptor, type 2 0.04400182 ZNF764 zinc finger protein 764 0.00620326 ADCK4 aarF domain containing kinase 4 0.02276393 EFHA1 EF-hand domain family, member Al 0.01216572 DIAPH3 diaphanous homolog 3 (Drosophila) 0.03802677 / 694375 6 .1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value KIF9 kinesin family member 9 1.346678 0.02665295 kelch repeat and BTB (POZ) domain KBTBD10 containing 10 1.346583 0.04517275 v-akt murine thymoma viral oncogene AKT2 homolog 2 1.346576 0.040245 ATPase, H+ transporting, lysosomal ATP6V1B1 56/58kDa, VI subunit Bl 1.345892 0.03333946 F12 coagulation factor XII (Hageman factor) 1.345592 0.0046184 KIF13A kinesin family member 13A 1.345497 0.00072713 TRBV7-2 T cell receptor beta variable 7-2 1.345457 0.00970627 SCLT1 sodium channel and clathrin linker 1 1.345172 0.02022515 ATP synthase, H+ transporting, mitochondrial ATP5S F0 complex, subunit s (factor B) 1.344751 0.01699017 NT5E 5'-nucleotidase, ecto (CD73) 1.344379 0.01792402 syntrophin, beta 1 (dystrophin-associated SNTB1 protein Al, 59kDa, basic component 1) 1.344235 0.03577983 C20orfl60 chromosome 20 open reading frame 160 1.34407 0.03316357 hairy/enhancer-of-split related with YRPW HEY2 motif 2 1.343975 0.03234805 SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.34362 0.04399927 DLL1 delta-like 1 (Drosophila) 1.343162 0.02388195 KRT81 keratin 81 1.342955 0.03566106 alveolar soft part sarcoma chromosome ASPSCR1 region, candidate 1 1.342913 0.03671779 LYPD4 LY6/PLAUR domain containing 4 1.342848 0.04666735 procollagen-lysine, 2-oxoglutarate 5- PLOD3 dioxygenase 3 1.342835 0.02428522 CES2 Carboxylesterase 2 (intestine, liver) 1.342819 0.01927775 TFF3 trefoil factor 3 (intestinal) 1.342781 0.03513944 protein disulfide isomerase family A, member PDIA5 5 1.34214 0.03101883 HSPG2 heparan sulfate proteoglycan 2 1.341774 0.03447131 KLHDC10 kelch domain containing 10 1.34146 0.04514183 RBM7 R A binding motif protein 7 1.341205 0.01218817 DENND1C DENN/MADD domain containing 1C 1.341178 0.03422802 ATG16 autophagy related 16-like 1 (S. ATG16L1 cerevisiae) 1.3411 1 0.03484506 TMEM35 transmembrane protein 35 1.340953 0.04831484 myocilin, trabecular meshwork inducible MYOC glucocorticoid response 1.340916 0.03716645 SMOC2 SPARC related modular calcium binding 2 1.340814 0.03545095 CDCA8 Cell division cycle associated 8 1.340746 0.04499828 ZNF433 zinc finger protein 433 1.340633 0.00429054 LOC339524 hypothetical LOC339524 1.339964 0.04932416 KIAA1383 KIAA1383 1.339459 0.00376021 FLJ43860 FLJ43860 protein 1.339306 0.02548869 TMEM187 transmembrane protein 187 1.338988 0.01389232 protein tyrosine phosphatase-like (proline PTPLA instead of catalytic arginine), member A 1.338969 0.037401 MTX2 metaxin 2 1.338733 0.0334663 DB1/ 69437 5 16.1 Supplemental Tabic 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value family with sequence similarity 73, member FAM73A A 1.338713 0.00397283 LCP1 lymphocyte cytosolic protein 1 (L-plastin) 1.338614 0.04071473 TET1 tet oncogene 1 1.338454 0.03052802 CCL16 chemokine (C-C motif) ligand 16 1.338375 0.02109751 POU2AF1 POU class 2 associating factor 1 1.338032 0.0241 1808 ZNF575 zinc finger protein 575 1.338017 0.0417702 DNAH1 1 dynein, axonemal, heavy chain 11 1.337979 0.01880007 von Willebrand factor A domain containing VWA5B1 5B1 1.337776 0.00609771 MAD1L1 MAD 1 mitotic arrest deficient-like 1 (yeast) 1.337675 0.0490912 family with sequence similarity 71, member FAM71F1 Fl 1.33763 0.00878194 TRAPPC9 N/A 1.337554 0.01651589 Clorf201 chromosome 1 open reading frame 201 1.337552 0.0498056 OR52E5 N/A 1.3375 0.03682626 polymerase (R A) III (DNA directed) POLR3C polypeptide C (62kD) 1.337476 0.01864437 PRMT3 protein arginine methyltransferase 3 1.337342 0.03303852 KIF17 kinesin family member 17 1.336691 0.01760912 LIPC lipase, hepatic 1.336691 0.0039318 ARMC4 armadillo repeat containing 4 1.336666 0.04505778 CCDC60 coiled-coil domain containing 60 1.336495 0.00361605 EGLN1 egl nine homolog 1 (C. elegans) 1.336453 0.03867409 CATSPER1 cation channel, sperm associated 1 1.336405 0.0332202 SETDB2 SET domain, bifurcated 2 1.336084 0.02125444 nucleolar complex associated 4 homolog (S. NOC4L cerevisiae) 1.335968 0.0161945 CDYL chromodomain protein, Y-like 1.335878 0.02791548 calcium/calmodulin-dependent protein kinase CAMK2B II beta 1.335812 0.04798184 methylenetetrahydrofolate dehydrogenase MTHFD2L (NADP+ dependent) 2-like 1.335717 0.04103293 IGHG2 N/A 1.335709 0.04491141 FBX024 F-box protein 24 1.335484 0.01 106863 PCBP1 poly(rC) binding protein 1 1.33547 0.01595027 MPDZ multiple PDZ domain protein 1.335134 0.04286986 protein phosphatase 2, regulatory subunit B', PPP2R5B beta 1.335088 0.02170275 family with sequence similarity 172, member FAM172A A 1.335005 0.02084294 COG2 component of oligomeric golgi complex 2 1.334892 0.04709598 ICMT isoprenylcysteine carboxyl methyltransferase 1.334878 0.03860215 KIAA0430 KIAA0430 1.334773 0.01020301 cyclin-dependent kinase inhibitor 2C (pi 8, CDKN2C inhibits CDK4) 1.33462 0.04260088 STIL SCL/TAL1 interrupting locus 1.334613 0.03388643 PRSS7 Protease, serine, 7 (enterokinase) 1.334333 0.01 142169 XRCC6BP 1 XRCC6 binding protein 1 1.334324 0.02789105 EPS8L3 EPS8-like 3 1.334213 0.04695945 DB1/ 6 943751 . 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value DNAL1 dynein, axonemal, light chain 1 0.00728948 MVP major vault protein 0.01031094 C14orfl53 chromosome 14 open reading frame 153 0.01271846 GPNMB glycoprotein (transmembrane) nmb 0.03873986 MRPL14 mitochondrial ribosomal protein L14 0.04564392 PRIM2 primase, DNA, polypeptide 2 (58kDa) 0.04472306 C12orf53 chromosome 12 open reading frame 53 0.04842264 ARRB1 arrestin, beta 1 0.04064721 MYOIE myosin IE 0.02617532 acyl-CoA synthetase long-chain family ACSLl member 1 1.332807 0.04712455 family with sequence similarity 48, member FAM48A A 0.03909798 NLR NLR family, pyrin domain containing 2 0.02016962 YTHDF1 YTH domain family, member 1 6.74E-05 TE TEK tyrosine kinase, endothelial 0.02096853 heterogeneous nuclear ribonucleoprotein U- HNRNPUL1 like 1 0.03824297 C17orf68 chromosome 17 open reading frame 68 0.01659617 COL4A6 collagen, type IV, alpha 6 0.02055205 ADAM 15 ADAM metallopeptidase domain 5 0.04166114 ZNF230 zinc finger protein 230 0.03172799 leucine-rich repeats and immunoglobulin-like LRIG1 domains 1 1.332089 0.02564779 major histocompatibility complex, class II, HLA-DOB DO beta 0.02622731 GST02 glutathione S-transferase omega 2 0.04470831 SIN3 homolog A, transcription regulator SIN3A (yeast) 0.02326265 CNT 1 contactin 1 0.0209712 TMPRSS3 transmembrane protease, serine 3 0.00957193 MAGEA4 melanoma antigen family A, 4 0.0305814 Cytidine monophosphate N-acetylneuraminic CMAS acid synthetase 1.330734 0.01823308 family with sequence similarity 156, member FAM156A A 0.03781504 SPG11 Spastic paraplegia 11 (autosomal recessive) 0.02444527 SLC26A10 solute carrier family 26, member 10 0.01287172 ASB7 ankyrin repeat and SOCS bo -containing 7 0.04772905 MPRIP myosin phosphatase Rho interacting protein 0.04741189 ZNF221 zinc finger protein 2 0.02107807 spen homolog, transcriptional regulator SPEN (Drosophila) 0.00217947 PMV phosphomevalonate kinase 0.04833547 Nephrosis 2, idiopathic, steroid-resistant NPHS2 (podocin) 0.02886971 SNAP23 synaptosomal-associated protein, 23kDa 0.03566571 MIPEP mitochondrial intermediate peptidase 0.02939542 UNC5CL unc-5 homolog C (C. elegans)-like 0.03819333 I PPL1 inositol polyphosphate phosphatase-like 1 0.00979076 1/6943 7 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value NCF2 neutrophil cytosolic factor 2 1.32983 0.03949076 DTX3L deltex 3-like (Drosophila) 1.329799 0.00180118 hCG 2020170 HCG2020170 1.329766 0.01539661 WDR25 WD repeat domain 25 1.329556 0.02098528 U C84A Unc-84 homolog A (C. elegans) 1.329388 0.00510734 PXMP4 peroxisomal membrane protein 4, 24kDa 1.329312 0.04663567 RHBG Rh family, B glycoprotein (gene/pseudogene) 1.329034 0.031 11524 ZHX1 zinc fingers and homeoboxes 1 1.328792 0.02722766 Smith-Magenis syndrome chromosome SMC 7L region, candidate 7-like 1.328557 0.0041 1243 protein associated with topoisomerase II PATL1 homolog 1 (yeast) 1.328315 0.03968027 SLC9A1 1 solute carrier family 9, member 11 1.328309 0.0193753 family with sequence similarity 105, member FAM 105A A 1.32814 0.00467247 PSRC1 proline/serine-rich coiled-coil 1 1.328033 0.04722541 dapper, antagonist of beta-catenin, homolog 3 DACT3 (Xenopus laevis) 1.327948 0.02331086 family with sequence similarity 38, member FAM38A A 1.327903 0.00802084 CDC2L1 N/A 1.327887 0.0153454 CCM2 Cerebral cavernous malformation 2 1.327782 0.02434867 Glycerophosphodiester pho sphodiesterase GDPD1 domain containing 1 1.32778 0.00292559 TRIM41 tripartite motif-containing 4 1 1.327768 0.01 154423 COL15A1 collagen, type XV, alpha 1 1.327586 0.020284 TMEM161B transmembrane protein 161B 1.32758 0.04183431 ACAD 11 acyl-CoA dehydrogenase family, member 11 1.32751 1 0.01857637 DPPA4 Developmental pluripotency associated 4 1.32749 0.00698447 PRR13 proline rich 3 1.327383 0.02554162 microtubule-associated protein, RP/EB MAPRE3 family, member 3 1.327354 0.03360774 NSUN4 NOP2/Sun domain family, member 4 1.327342 0.03660922 ZNF500 zinc finger protein 500 1.327317 0.00726811 membrane-spanning 4-domains, subfamily A, MS4A14 member 14 1.327271 0.02715879 MBD6 methyl-CpG binding domain protein 6 1.326963 0.01599676 MCTP2 multiple C2 domains, transmembrane 2 1.326518 0.04849203 ATP-binding cassette, sub-family C ABCC9 (CFTR/MRP), member 9 1.326231 0.03610157 EHF ets homologous factor 1.326027 0.04824006 GIF gastric intrinsic factor (vitamin B synthesis) 1.325988 0.01793027 SLC24A5 Solute carrier family 24, member 5 1.325788 0.02700464 ZNF282 zinc finger protein 282 1.325592 0.04251978 ICAIL islet cell autoantigen l,69kDa-like 1.325277 0.01671185 PLG plasminogen 1.325181 0.02059755 ZNF461 zinc finger protein 46 1.325137 0.03479437 C14orfl78 chromosome 14 open reading frame 178 1.325086 0.03532542 AN RD53 ankyrin repeat domain 53 1.325033 0.0308792 ZNF318 zinc finger protein 318 1.324888 0.04057492 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Ceils Gene Symbol Gene Description Fold Ttest P Change value KIF20B kinesin family member 20B 0.00916296 CT45A2 cancer/testis antigen family 45, member A2 0.01496868 TRIML2 tripartite motif family-like 2 0.02904986 FBX05 F-box protein 5 0.0080861 1 serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding SERPINH1 protein 1) 0.01919945 HAUS5 HAUS augmin-like complex, subunit 5 0.00324377 PKD1L2 polycystic kidney disease 1-like 2 0.03252629 Chromodomain helicase DNA binding protein CHD5 5 0.03775408 ADAM metallopeptidase domain 19 (meltrin ADAM 19 beta) 0.01218115 CCR4-NOT transcription complex, subunit 6- CNOT6L like 0.01210832 KCNT2 Potassium channel, subfamily T, member 2 0.04130177 HORMAD2 HORMA domain containing 2 0.04105609 PEX6 peroxisomal biogenesis factor 6 0.00710564 CCDC79 coiled-coil domain containing 79 0.03779917 BTN3A2 butyrophilin, subfamily 3, member A2 0.04746066 C9orf9 chromosome 9 open reading frame 9 0.00782996 adaptor-related protein complex 4, epsilon 1 AP4E1 subunit 0.00619788 ATN1 atrophin 1 0.02343773 C18orf22 chromosome 18 open reading frame 22 0.04587944 LEPR leptin receptor 0.04430447 MED1 mediator complex subunit 1 0.04246086 C10orf4 Chromosome 10 open reading frame 4 0.01735236 benzodiazapine receptor (peripheral) BZRAP1 associated protein 1 0.03558951 HS6ST1 heparan sulfate 6-O-sulfotransferase 1 0.01662026 latent transforming growth factor beta binding LTBP4 protein 4 0.0357762 MANBA mannosidase, beta A, lysosomal 0.0144055 TBC1 domain family, member 8B (with TBC1D8B GRAM domain) 1.321661 0.02024654 acyl-CoA synthetase bubblegum family ACSBG2 member 2 0.02038367 PMS2L5 postmeiotic segregation increased 2-like 5 0.04674914 Asthma-associated alternatively spliced gene AAA1 1 0.0125656 TOP3B topoisomerase (DNA) III beta 0.0448924 ZBTB44 zinc finger and BTB domain containing 44 0.00360563 SMO smoothened homolog (Drosophila) 0.03439192 ectonucleoside triphosphate ENTPD3 diphosphohydrolase 3 0.01633764 MSLN mesothelin 0.03681721 WDR72 WD repeat domain 72 0.02144796 TMEM144 transmembrane protein 144 0.01405535 MED7 mediator complex subunit 7 0.04881557 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value aryl hydrocarbon receptor nuclear ARNTL translocator-like 1.320026 0.01245522 protein tyrosine phosphatase, non-receptor PTPN23 type 23 1.320026 0.00645288 FSTL4 follistatin-like 4 1.319819 0.02501339 TMEM219 transmembrane protein 219 1.319745 0.02673344 phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, GART phosphoribosylaminoimidazole synthetase 1.31974 0.04033209 PHKA2 phosphorylase kinase, alpha 2 (liver) 1.31943 0.04301 133 DMGDH dimethylglycine dehydrogenase 1.319296 0.03413839 C14orfl47 chromosome 14 open reading frame 147 1.319192 0.03875552 TRIM22 tripartite motif-containing 22 1.319187 0.04164827 glutamic pyruvate transaminase (alanine GPT2 aminotransferase) 2 1.31914 0.00699189 SSH1 slingshot homolog 1 (Drosophila) 1.318798 0.0307019 E B embigin homolog (mouse) 1.318438 0.03974458 MSTOl misato homolog 1 (Drosophila) 1.318428 0.01888897 PRKCQ protein kinase C, theta 1.318396 0.03206098 ADAM metallopeptidase with ADAMTS13 thrombospondin type 1 motif, 13 1.318309 0.02353973 PDRG1 p53 and DNA-damage regulated 1 1.318285 0.04255131 SNRK SNF related kinase 1.318247 0.02386553 C9orfl00 chromosome 9 open reading frame 100 1.318221 0.01355025 TR M 6 tripartite motif-containing 56 1.318199 0.03539142 GCNT1 glucosaminyl (N-acetyl) transferase 1, core 2 1.318145 0.0106976 ARHGEF5L N/A 1.318054 0.03589274 CPNE7 copine VII 1.318018 0.04033407 UBE2S ubiquitin-conjugating enzyme E2S 1.317991 0.03399721 ZNF321 Zinc finger protein 321 1.317951 0.03230609 ZNF143 zinc finger protein 143 1.317349 0.04315744 RNF144B ring finger protein 144B 1.317336 0.00626051 USP24 ubiquitin specific peptidase 24 1.317279 0.04933808 Clorfl22 chromosome 1 open reading frame 122 1.317239 0.02093694 ZFP28 zinc finger protein 28 homolog (mouse) 1.3171 18 0.00740862 GUCY1B3 guanylate cyclase 1, soluble, beta 3 1.317051 0.00086926 PRDM16 PR domain containing 16 1.317007 0.04796125 KCP kielin/chordin-like protein 1.316988 0.0088902 PCSK5 proprotein convertase subtilisin/kexin type 5 1.316956 0.01056173 BCL2/adenovirus E1B 19kD interacting BNIPL protein like 1.316952 0.03989385 solute carrier family 22 (organic anion/urate SLC22A12 transporter), member 12 1.31688 0.04811674 RAI2 retinoic acid induced 2 1.316758 0.03820596 OLFML2B olfactomedin-like 2B 1.31662 0.01997839 C8orf45 chromosome 8 open reading frame 45 1.316541 0.04426162 KLKB1 kallikrein B, plasma (Fletcher factor) 1 1.316373 0.0385414 TEX14 testis expressed 14 1.316226 0.03827991 PON3 paraoxonase 3 1.315951 0.03474527 / 694375 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value DOCK4 dedicator of cytokinesis 4 1.315887 0.02646044 nuclear factor of kappa light polypeptide gene NFKBIL2 enhancer in B-cells inhibitor-like 2 1.315349 0.01640883 CCNB1 cyclin B l 1.315053 0.02415274 RNF213 ring finger protein 213 1.31469 0.00272093 CDH9 cadherin 9, type 2 (Tl-cadherin) 1.314628 0.0156202 solute carrier family 15 (H+/peptide SLC15A2 transporter), member 2 1.314537 0.01002407 GPATCH8 G patch domain containing 8 1.314467 0.03038614 IRX1 iroquois homeobox 1 1.313925 0.01156482 LPHN2 latrophilin 2 1.313747 0.00687677 TMEM146 transmembrane protein 146 1.313705 0.02082781 CDK3 cyclin-dependent kinase 3 1.313305 0.01672594 low density lipoprotein receptor-related LRP2 protein 2 1.313296 0.00968269 TG thyroglobulin 1.313285 0.00185045 GPR 1 1 G protein-coupled receptor 1 1.313243 0.04135709 C14orfl45 chromosome 14 open reading frame 145 1.312749 0.03212212 growth factor independent 1 transcription GFI1 repressor 1.312642 0.01046655 EIF4H eukaryotic translation initiation factor 4H 1.312594 0.00452783 ACPP acid phosphatase, prostate 1.312577 0.03492758 nudix (nucleoside diphosphate linked moiety NUDT15 X)-type motif 15 1.312551 0.04340014 ArfGAP with SH3 domain, ankyrin repeat ASAP3 and PH domain 3 1.312499 0.03870607 PIAS3 protein inhibitor of activated STAT, 3 1.312445 0.02652922 PAN3 poly(A) specific ribonuclease subunit PAN3 homolog (S. cerevisiae) 1.312377 0.01230948 radial spoke head 0 homolog B RSPH10B (Chlamydomonas) 1.31191 1 0.01401368 UROC1 urocanase domain containing 1 1.311867 0.04595685 C6orfl82 Chromosome 6 open reading frame 2 1.311566 0.02633846 S100A7 S100 calcium binding protein A7 1.31 1542 0.0142408 myosin, heavy chain 8, skeletal muscle, MYH8 perinatal 1.31 154 0.0245483 LMX1B LIM homeobox transcription factor 1, beta 1.311513 0.02368958 AHCYL2 adenosylhomocysteinase-like 2 1.311322 0.04070981 CCDC135 coiled-coil domain containing 135 1.31 1143 0.02857 WHSC2 Wolf-Hirschhorn syndrome candidate 2 1.311082 0.03526217 COL8A2 collagen, type VIII, alpha 2 1.310946 0.02539666 Usher syndrome 2A (autosomal recessive, USH2A mild) 1.310913 0.04391246 ORAOV1 Oral cancer overexpressed 1 1.310757 0.01014515 NUP35 nucleoporin 35kDa 1.310688 0.03504381 calcium channel, voltage-dependent, T type, CACNA1I alpha 11 subunit 1.310393 0.02761535 SCARA3 scavenger receptor class A, member 3 1.310298 0.04660373 queuine tRNA-ribosyltransferase domain QTRTD1 containing 1 1.310073 0.03897065 )B 17694375 16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value ADAL adenosine deaminase-like 1.309891 0.0379593 PRMT7 protein arginine methyltransferase 7 1.309419 0.01323269 prematurely terminated mRNA decay factor¬ LOC91431 like 1.309402 0.04138642 I ADL InaD-like (Drosophila) 1.309387 0.00981621 SYS1 Golgi-localized integral membrane SYS1 protein homolog (S. cerevisiae) 1.30937 0.0448041 kelch repeat and BTB (POZ) domain KBTBD11 containing 11 1.309312 0.01421923 TMEM107 transmembrane protein 107 1.309287 0.01 165641 ATPase, H+/K+ exchanging, alpha ATP4A polypeptide 1.309252 0.03384388 C4orf35 chromosome 4 open reading frame 35 1.309181 0.00329241 family with sequence similarity 55, member FAM55A A 1.309086 0.02141947 SNIP1 Smad nuclear interacting protein 1 1.30902 0.04305763 potassium voltage-gated channel, KQT-like KCNQ5 subfamily, member 5 1.308923 0.01452584 solute carrier family 20 (phosphate SLC20A1 transporter), member 1 1.308554 0.01655305 ZNF479 zinc finger protein 479 1.308537 0.03375878 TCN2 transcobalamin II 1.308533 0.01433225 MUT methylmalonyl CoA mutase 1.308487 0.02319145 IRF1 interferon regulatory factor 1 1.308463 0.04031537 testis-specific transcript, Y-linked 14 (non TTTY14 protein coding) 1.308338 0.02764961 MGC4294 hypothetical protein MGC4294 1.308291 0.00833659 HK3 hexokinase 3 (white cell) 1.307948 0.00984782 CNP 2',3'-cyclic nucleotide 3' phosphodiesterase 1.307669 0.03190761 ARHGAP19 Rho GTPase activating protein 9 1.307466 0.02820484 BOC Boc homolog (mouse) 1.307464 0.04120587 HPSE2 heparanase 2 1.307142 0.02069281 HOXA1 1 homeobox A l 1 1.3071 17 0.02978879 IGSF8 immunoglobulin superfamily, member 8 1.307107 0.04802534 APAF1 apoptotic peptidase activating factor 1 1.306905 0.03041618 GJA8 gap junction protein, alpha 8, 50kDa 1.306617 0.0301685 ENG endoglin 1.306576 0.03736587 PCNA proliferating cell nuclear antigen 1.306526 0.02897492 ZNF234 zinc finger protein 234 1.30646 0.01321066 latent transforming growth factor beta binding LTBP3 protein 3 1.306433 0.02949493 PRDM4 PR domain containing 4 1.30643 0.04352244 INSL5 insulin-like 5 1.306233 0.01876093 JMJD8 jumonji domain containing 8 1.306173 0.04275968 DnaJ (Hsp40) homolog, subfamily C, member DNAJC28 28 1.306141 0.0464148 RNF123 ring finger protein 123 1.305908 0.0316032 TEKT1 tektin 1 1.305715 0.01698729 ETN 1 ethanolamine kinase 1 1.305688 0.01828431 PPP2R2D protein phosphatase 2, regulatory subunit B, 1.305577 0.0421285 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value delta isoform large subunit GTPase 1 homolog (S. LSG1 cerevisiae) 1.30556 0.02208307 CD40 molecule, TNF receptor superfamily CD40 member 5 1.305475 0.029036 sulfotransferase family, cytosolic, 1C, SULT1C4 member 4 1.305438 0.0172204 TMEM190 transmembrane protein 190 1.305362 0.01501063 polymerase (RNA) III (DNA directed) POLR3D polypeptide D, 44kDa 1.30532 0.01376665 amylo-alpha-1, 6-glucosidase, 4-alpha- AGL glucanotransferase 1.305308 0.02445334 pleckstrin homology domain containing, PLEKHG6 family G (with RhoGef domain) member 6 1.305225 0.00992449 xenotropic and polytropic retrovirus receptor XPR1 1 1.305053 0.00184251 ankyrin repeat and BTB (POZ) domain ABTB2 containing 2 1.305043 0.02396353 TGM5 transglutaminase 5 1.304837 0.02979951 CDC25B cell division cycle 25 homolog B (S. pombe) 1.304806 0.03726143 TMOD2 tropomodulin 2 (neuronal) 1.30475 0.01772342 TMEM185B transmembrane protein 185B (pseudogene) 1.30461 0.00257445 PHKA1 phosphorylase kinase, alpha 1 (muscle) 1.304453 0.047388 COL19A1 collagen, type XIX, alpha 1 1.304251 0.01 176413 SLC26A6 solute carrier family 26, member 6 1.304206 0.01790112 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein PPFIA2 (liprin), alpha 2 1.304138 0.04810995 PN D Paroxysmal nonkinesigenic dyskinesia 1.304131 0.02809504 Rap guanine nucleotide exchange factor RAPGEF4 (GEF) 4 1.303909 0.02695454 NLGN4X neuroligin 4, X-linked 1.303813 0.03148034 CLCA1 chloride channel accessory 1 1.303717 0.03919733 polymerase (RNA) II (DNA directed) POLR2I polypeptide I, 14.5kDa 1.303374 0.04830243 C14orf48 chromosome 1 open reading frame 48 1.303225 0.00358584 VILL villin-like 1.302715 0.04757931 membrane associated guanylate kinase, WW MAGI2 and PDZ domain containing 2 1.30264 0.02027315 cytochrome P450, family 2, subfamily B, CYP2B6 polypeptide 6 1.30263 0.01340493 LATS, large tumor suppressor, homolog 1 LATS1 (Drosophila) 1.3025 0.03933197 DOK5 docking protein 5 1.302469 0.01233959 ACACA acetyl-CoA carboxylase alpha 1.302373 0.02462743 PRKD3 protein kinase D3 1.302343 0.04005699 DAPK3 death-associated protein kinase 3 1.302229 0.03626214 C5orfl3 chromosome 5 open reading frame 13 1.302196 0.04509051 WWOX WW domain containing oxidoreductase 1.302119 0.02600082 FA2H fatty acid 2-hydroxylase 1.302021 0.02502105 DBl/ 694375 16.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value PKN3 protein kinase N3 1.30192 0.0296009 STEAP3 STEAP family member 3 1.301879 0.0185418 MYPN myopalladin 1.301792 0.04028135 PSD pleckstrin and Sec7 domain containing 1.301792 0.00332964 TOX high mobility group box family member TOX2 2 1.301788 0.00829846 CDC7 cell division cycle 7 homolog (S. cerevisiae) 1.301589 0.03056512 RWDD1L1 N/A 1.301455 0.00671015 SP9 Sp9 transcription factor homolog (mouse) 1.301235 0.04540898 vacuolar protein sorting 4 1 homolog (S. VPS41 cerevisiae) 1.301232 0.03671784 sarcoglycan, delta (35kDa dystrophin- SGCD associated glycoprotein) 1.301221 0.02934646 TRIM36 tripartite motif-containing 36 1.301203 0.01262691 PRR4 proline rich 4 (lacrimal) 1.301132 0.03615856 DnaJ (Hsp40) homolog, subfamily B, member DNAJB12 12 1.300681 0.04334606 origin recognition complex, subunit 3-like ORC3L (yeast) 1.300652 0.01020332 NIMA (never in mitosis gene a)- related NEK 10 kinase 10 1.300415 0.01710128 translocase of inner mitochondrial membrane TIMM50 50 homolog (S. cerevisiae) 1.300325 4.55E-05 PCDHGA8 protocadherin gamma subfamily A, 8 1.300313 0.02404996 TECPR1 tectonin beta-propeller repeat containing 1 1.300191 0.03405406 ZNF789 zinc finger protein 789 1.300153 0.03424549 MKRN1 makorin ring finger protein 1 1.299966 0.01476264 MLF1IP MLF1 interacting protein 1.29929 0.03391614 GPR45 G protein-coupled receptor 45 1.29928 0.04904797 progestin and adipoQ receptor family member PAQR5 V 1.299268 0.00317122 FHDC1 FH2 domain containing 1 1.299248 0.02931807 eukaryotic translation elongation factor 1 EEF1D delta (guanine nucleotide exchange protein) 1.299174 0.02232024 SPAG16 sperm associated antigen 16 1.299145 0.02531261 ZNF175 zinc finger protein 175 1.299129 0.02599533 MSR1 macrophage scavenger receptor 1 1.298769 0.02013449 THOC3 THO complex 3 1.298749 0.02818972 solute carrier family 12 (sodium/chloride SLC12A3 transporters), member 3 1.298657 0.04427049 TMEM175 transmembrane protein 175 1.298598 0.00703759 eukaryotic translation initiation factor 2-alpha EIF2AK3 kinase 3 1.298331 0.04888608 TSSC1 tumor suppressing subtransferable candidate 1 1.298268 0.04784076 dihydrolipoamide branched chain transacylase DBT E2 1.298264 0.03189072 DnaJ (Hsp40) homolog, subfamily C, member DNAJC14 14 1.297893 0.04993902 SPAG4L Sperm associated antigen 4-like 1.297362 0.00528533 MCC mutated in colorectal cancers 1.297264 0.02171935 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value COP9 constitutive photomorphogenic COPS7A homolog subunit 7A (Arabidopsis) 1.297234 0.01501032 MRT04 mRNA turnover 4 homolog (S. cerevisiae) 1.29723 0.02704754 RHD Rh blood group, D antigen 1.297189 0.02262032 TYR03 TYR03 protein tyrosine kinase 1.297133 0.04325744 ATF6 activating transcription factor 6 1.297079 0.042571 11 DUSP15 dual specificity phosphatase 15 1.297006 0.02529751 LOC541473 FK506 binding protein 6, 36kDa pseudogene 1.296923 0.00600023 CEND1 cell cycle exit and neuronal differentiation 1 1.296588 0.04442424 interferon regulatory factor 2 binding protein IRF2BP1 1 1.296464 0.0403163 TMEM179 transmembrane protein 1 9 1.296444 0.0217629 SPATA12 spermatogenesis associated 12 1.296108 0.01940578 Olfactory receptor, family 2, subfamily , OR2W5 member 5 1.296004 0.04316118 GIGYF1 GRB10 interacting GYF protein 1 1.295491 0.03956304 YEATS4 YEATS domain containing 4 1.295452 0.03794617 solute carrier family 10 (sodium/bile acid SLC10A7 cotransporter family), member 7 1.295385 0.0235016 C17orf55 chromosome 17 open reading frame 55 1.295284 0.0171084 INVS inversin 1.295193 0.00903241 SLC46A3 solute carrier family 46, member 3 1.295174 0.04864538 EMILIN1 elastin microfibril interfacer 1 1.295009 0.0181214 NAALAD2 N-acetylated alpha-linked acidic dipeptidase 2 1.294984 0.0325433 STAB2 stabilin 2 1.294843 0.02909169 CCDC141 coiled-coil domain containing 141 1.294841 0.03543174 PFDN2 prefoldin subunit 2 1.294826 0.02783804 PGM1 phosphoglucomutase 1 1.294817 0.04011517 wingless-type MT V integration site family, WNT2B member 2B 1.294816 0.01338583 ArfGAP with coiled-coil, ankyrin repeat and ACAPI PH domains 1 1.294712 0.00969179 UFC1 ubiquitin-fold modifier conjugating enzyme 1 1.294642 0.04198936 MCF.2 cell line derived transforming MCF2 sequence 1.294591 0.04438568 MAGEB3 melanoma antigen family B, 3 1.294585 0.01466257 v-src sarcoma (Schmidt-Ruppin A-2) viral SRC oncogene homolog (avian) 1.294388 0.02949684 POLH polymerase (DNA directed), eta 1.293916 0.048091 13 HAP1 huntingtin-associated protein 1 1.293825 0.01962217 runt-related transcription factor 1; RUNX1T1 translocated to, 1 (cyclin D-related) 1.293798 0.00514469 TP53BP2 tumor protein p53 binding protein, 2 1.293725 0.00778505 ESRP2 epithelial splicing regulatory protein 2 1.293654 0.00638682 CRIP3 Cysteine-rich protein 3 1.293478 0.00371955 A2M alpha-2-macroglobulin 1.293429 0.00961782 CCDC114 coiled-coil domain containing 114 1.293346 0.03959844 DnaJ (Hsp40) homolog, subfamily B, member DNAJB2 2 1.293323 0.00219792 SLC25A40 solute carrier family 25, member 40 1.293282 0.03909541 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SPINT2 serine peptidase inhibitor, Kunitz type, 2 1.293191 0.04918457 HIF3A Hypoxia inducible factor 3, alpha subunit 1.293096 0.04351659 TGFBR1 transforming growth factor, beta receptor 1 1.293066 0.01642541 TRIM49 tripartite motif-containing 49 1.293012 0.01757071 NADH dehydrogenase (ubiquinone) 1 alpha NDUFA10 subcomplex, 10, 42kDa 1.292946 0.04491656 cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, CFTR member 7) 1.292942 0.01840615 BAT4 HLA-B associated transcript 4 1.292895 0.02567915 amyloid beta (A4) precursor protein-binding, APBB1 family B, member 1 (Fe65) 1.292641 0.01662514 RBM25 RNA binding motif protein 25 1.292556 0.04894338 HERPUD2 HERPUD family member 2 1.292034 0.04837984 MAP2K2 mitogen-activated protein kinase kinase 2 1.291915 0.00765513 AKAP8L A kinase (PRKA) anchor protein 8-like 1.291794 0.04370944 RREBl ras responsive element binding protein 1 1.291689 0.00827326 FAM53C family with sequence similarity 53, member C 1.291657 0.01840381 MSH5 mutS homolog 5 (E. coli) 1.291503 0.00094657 EFR3B EFR3 homolog B (S. cerevisiae) 1.291499 0.03382682 MGC24975 Hypothetical protein MGC24975 1.291206 0.01978755 MAN1B1 mannosidase, alpha, class IB, member 1 1.290923 0.03761272 KRT7 keratin 7 1.290891 0.04257891 RBP3 retinol binding protein 3, interstitial 1.290772 0.00495777 NLRP4 NLR family, pyrin domain containing 4 1.290637 0.03772813 CHDH choline dehydrogenase 1.290568 0.02570163 C14orf83 chromosome 14 open reading frame 83 1.290438 0.03660187 SOX30 SRY (sex determining region Y)-box 30 1.290387 0.02018918 MGC21881 hypothetical locus MGC21881 1.290175 0.03433103 HNMT histamine N-methyltransferase 1.290102 0.00921103 KIF24 Kinesin family member 24 1.290062 0.03501299 GPR176 G protein-coupled receptor 176 1.289767 0.04432081 SFRS16 splicing factor, arginine/serine-rich 6 1.289527 0.00918842 PDE3B phosphodiesterase B, cGMP-inhibited 1.2891 1 0.02490519 ATP-binding cassette, sub-family C ABCC10 (CFTR/MRP), member 10 1.28892 0.00730162 olfactory receptor, family 2, subfamily C, OR2C3 member 3 1.288831 0.04451079 calcium/calmodulin-dependent protein kinase CAMKK2 kinase 2, beta 1.288582 0.00401144 HBXIP hepatitis B virus x interacting protein 1.288507 0.03684191 FERMT1 fermitin family homolog 1 (Drosophila) 1.288475 0.01992465 PCSK2 proprotein convertase subtilisin/kexin type 2 1.288199 0.01907613 cysteine-rich secretory protein LCCL domain CRISPLD1 containing 1 1.288049 0.02520263 complement component 1, q subcomponent, C1QB B chain 1.287998 0.00958669 MGC29506 plasma cell-induced ER protein 1 1.287906 0.03621649 guanine nucleotide binding protein (G GNG5 protein), gamma 5 1.287847 0.0044331 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value MAGED1 melanoma antigen family D, 1 1.287519 0.02569332 CASKIN2 CASK interacting protein 2 1.287506 0.03214233 mitogen-activated protein kinase kinase MAP3K1 1 kinase 1 1.287394 0.00590728 C12orf27 chromosome 1 open reading frame 27 1.287284 0.03594103 SMEK homolog 3, suppressor of mekl SMEK3P (Dictyostelium) pseudogene 1.287218 0.01213296 C8orf41 chromosome 8 open reading frame 4 1 1.287147 0.02624243 StAR-related lipid transfer (START) domain STARD3 containing 3 1.287005 0.02329359 RPL14 ribosomal protein LI 1.286996 0.04389132 ELMOD3 ELMO/CED-12 domain containing 3 1.286807 0.02853122 KIAA0513 KIAA0513 1.286421 0.03234515 DIDOl death inducer-obliterator 1 1.28637 0.02217596 SLC43A3 solute carrier family 43, member 3 1.286291 0.00818887 NPC2 Niemann-Pick disease, type C2 1.286232 0.01035146 SIGLEC8 sialic acid binding Ig-like lectin 8 1.285973 0.0432303 core-binding factor, runt domain, alpha CBFA2T2 subunit 2; translocated to, 2 1.28571 0.00793092 MYH6 myosin, heavy chain 6, cardiac muscle, alpha 1.285655 5.89E-05 C12orf63 chromosome 12 open reading frame 63 1.285351 0.02001726 SHOX2 short stature homeobox 2 1.285337 0.01608284 IFLTD1 intermediate filament tail domain containing 1 1.285219 0.0251623 CT45A5 cancer/testis antigen family 45, member A5 1.285076 0.02092369 CDC42 effector protein (Rho GTPase CDC42EP4 binding) 4 1.284956 0.01468179 required for meiotic nuclear division 5 RMND5A homolog A (S. cerevisiae) 1.284948 0.01304799 FBXW2 F-box and WD repeat domain containing 2 1.284946 0.03658627 VHL von Hippel-Lindau tumor suppressor 1.284754 0.00453337 MYOM2 myomesin (M-protein) 2, 165kDa 1.284592 0.03781633 CDK5 regulatory subunit associated protein CDKAL1 1-like 1 1.28459 0.00136589 integrin, alpha X (complement component 3 ITGAX receptor 4 subunit) 1.284505 0.01564835 sema domain, immunoglobulin domain (Ig), SEMA3E short basic domain, secreted, (semaphorin) 3E 1.284324 0.00568937 chondroitin sulfate proteoglycan 5 CSPG5 (neuroglycan C) 1.284094 0.0016048 DPP9 dipeptidyl-peptidase 9 1.284052 0.04672429 EXOC3 exocyst complex component 3 1.284045 0.04170658 phosphatidylinositol glycan anchor PIGN biosynthesis, class N 1.283912 0.01937258 selectin P (granule membrane protein SELP 140kDa, antigen CD62) 1.283742 0.0326095 CGB1 chorionic gonadotropin, beta polypeptide 1 1.283709 0.04475474 PCDHA1 protocadherin alpha 1 1.283621 0.0032591 STK1 1IP serine/threonine kinase 11 interacting protein 1.283586 0.04232222 phosphoinositide kinase, FYVE finger PIKFYVE containing 1.283542 0.02186269 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value AGFG2 ArfGAP with FG repeats 2 1.283524 0.04847402 cleavage stimulation factor, 3' pre-RNA, CSTF2 subunit 2, 64kDa 1.283423 0.02479593 MTCP1 mature T-cell proliferation 1 1.283365 0.02616361 HDGF hepatoma-derived growth factor 1.283264 0.03225054 SLC38A9 solute carrier family 38, member 9 1.283074 0.01870351 UROD uroporphyrinogen decarboxylase 1.283017 0.00763977 CRX cone-rod homeobox 1.282794 0.04267342 C5orf42 chromosome 5 open reading frame 42 1.282748 0.01191994 TPMT thiopurine S-methyltransferase 1.282727 0.0166767 TLR3 toll-like receptor 3 1.282615 0.01532234 FHL1 four and a half LIM domains 1 1.282345 0.00644461 CNK5 potassium channel, subfamily K, member 5 1.282262 0.0289603 PLAC4 placenta-specific 4 1.2821 13 0.01069166 guanylate cyclase 2C (heat stable enterotoxin GUCY2C receptor) 1.281951 0.01787448 CABIN 1 calcineurin binding protein 1 1.28167 0.03449354 BMF Bcl2 modifying factor 1.281669 0.01524191 CCDC68 coiled-coil domain containing 68 1.281411 0.04189215 DYM dymeclin 1.281358 0.03128598 ZNF804B zinc finger protein 804B 1.281045 0.01404671 Clorf228 chromosome 1 open reading frame 228 1.280803 0.01893027 pro-platelet basic protein (chemokine (C-X-C PPBP motif) ligand 7) 1.280777 0.01782109 XCL1 chemokine (C motif) ligand 1 1.280574 0.04413665 translocase of outer mitochondrial membrane TOMM40L 40 homolog (yeast)-like 1.280371 0.02338092 RASGEFIC RasGEF domain family, member 1C 1.280162 0.0280827 JPH4 junctophilin 4 1.28015 0.04280613 family with sequence similarity 54, member FAM54A A 1.279955 0.03734787 potassium channel tetramerisation domain KCTD5 containing 5 1.27975 0.02869465 Olfactory receptor, family 13, subfamily C, OR13C2 member 2 1.279711 0.03442259 ZC3H18 zinc finger CCCH-type containing 18 1.27964 0.04636705 CAPN10 calpain 10 1.279257 0.00198792 ING5 inhibitor of growth family, member 5 1.27892 0.04661732 RGS8 regulator of G-protein signaling 8 1.278832 0.00174233 AC02 aconitase 2, mitochondrial 1.27882 0.04484345 FKBP10 FK506 binding protein 10, 65 kDa 1.278655 0.0175814 Olfactory receptor, family 6, subfamily C, OR6C3 member 3 1.27861 1 0.01752476 RCAN2 regulator of calcineurin 2 1.278387 0.03588298 PGCP plasma glutamate carboxypeptidase 1.2781 0.01883749 TERT telomerase reverse transcriptase 1.278023 0.01279226 ADAM28 ADAM metallopeptidase domain 28 1.277873 0.00355689 fibroblast growth factor 9 (glia-activating FGF9 factor) 1.277817 0.03562992 SIGLEC7 sialic acid binding Ig-like lectin 7 1.277801 0.04178277 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value CD300A CD300a molecule 1.27763 0.01498091 FRMD3 FERM domain containing 3 1.277627 0.01554986 Cllorf39 chromosome 1 open reading frame 39 1.277453 0.00448246 KIAA1772 KIAA1772 1.277126 0.03375901 wingless-type MMTV integration site family, W T5B member 5B 1.27708 0.0226936 HHATL hedgehog acyltransferase-like 1.277057 0.04379471 MDC1 mediator of DNA-damage checkpoint 1 1.27701 1 0.03028642 DDR2 discoidin domain receptor tyrosine kinase 2 1.276973 0.03395236 Rap guanine nucleotide exchange factor RAPGEF1 (GEF) 1 1.276884 0.01192098 ELK3, ETS-domain protein (SRF accessory ELK3 protein 2) 1.276704 0.00360868 CFH complement factor H 1.276522 0.01729259 KIF6 Kinesin family member 6 1.275939 0.00729677 PALLD palladin, cytoskeletal associated protein 1.275797 0.00096629 ZNF512 zinc finger protein 512 1.275728 0.04504732 aldehyde dehydrogenase 6 family, member ALDH16A1 Al 1.275703 0.04010194 WDR23 WD repeat domain 23 1.275664 0.00341463 SLC47A1 solute carrier family 47, member 1 1.275285 0.04228358 CCDC132 coiled-coil domain containing 132 1.275185 0.02473214 IMPACT Impact homolog (mouse) 1.275025 0.03467059 HPSE heparanase 1.274968 0.03689874 LHX6 LIM homeobox 6 1.274965 0.01865077 major facilitator superfamily domain MFSD8 containing 8 1.27465 0.02330326 osteoclast associated, immunoglobulin-like OSCAR receptor 1.27438 0.02518541 BMP2K BMP2 inducible kinase 1.274379 0.04885737 Olfactory receptor, family 8, subfamily S, OR8S1 member 1 1.274174 0.03604905 ZNF329 Zinc finger protein 329 1.274083 0.04612534 GATA5 GATA binding protein 5 1.273996 0.00282524 FHL2 four and a half LIM domains 2 1.273898 0.00514596 polycystic kidney disease 1 (autosomal PKD1 dominant) 1.273857 0.00447694 WDR33 WD repeat domain 33 1.273789 0.00149716 KIAA0831 KIAA0831 1.273734 0.04652461 SP110 SP1 10 nuclear body protein 1.273585 0.00042015 STIM2 stromal interaction molecule 2 1.273451 0.02757475 CNPY4 canopy 4 homolog (zebrafish) 1.273357 8.71E-05 N-acylsphingosine amidohydrolase (acid ASAH1 ceramidase) 1 1.273185 0.03366104 GYPB glycophorin B (M S blood group) 1.273166 0.00262253 origin recognition complex, subunit 1-like ORC1L (yeast) 1.273124 0.03331651 FES feline sarcoma oncogene 1.273069 0.04620132 CNGB1 cyclic nucleotide gated channel beta 1 1.272862 0.0377707 VPS13D vacuolar protein sorting 13 homolog D (S. 1.272795 0.0243252 >B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value cerevisiae) NAPSA napsin A aspartic peptidase 1.272758 0.03131851 EPB41L3 Erythrocyte membrane protein band 4.1 -like 3 1.27261 1 0.03658226 ANKRD23 ankyrin repeat domain 23 1.272549 0.02940823 PFTK1 PFTAIRE protein kinase 1 1.272423 0.01977383 budding uninhibited by benzimidazoles 1 BUB1 homolog (yeast) 1.272392 0.01439459 calcium channel, voltage-dependent, T type, CACNA1G alpha 1G subunit 1.27238 0.03676087 solute carrier family 7 (cationic amino acid SLC7A7 transporter, y+ system), member 7 1.272137 0.00085848 FLJ43826 FLJ43826 protein 1.271965 0.03776522 DAP3 death associated protein 3 1.271808 0.02339598 ral guanine nucleotide dissociation stimulator¬ RGL2 like 2 1.271306 0.0133294 SEC16B SEC 16 homolog B (S. cerevisiae) 1.27129 0.01950576 caspase 10, apoptosis-related cysteine CASP 10 peptidase 1.271252 0.01758932 SEPP1 selenoprotein P, plasma, 1 1.271193 0.01057495 interleukin 16 (lymphocyte chemoattractant IL16 factor) 1.270979 0.03838038 KRT222P Keratin 222 pseudogene 1.270266 0.01755372 DOCK9 dedicator of cytokinesis 9 1.270219 0.03743694 ZNF45 zinc finger protein 45 1.269929 0.00158253 CTNNA3 Catenin (cadherin-associated protein), alpha 3 1.269856 0.01638294 C20orfl2 chromosome 20 open reading frame 12 1.269786 0.02471881 PLXNA2 plexin A2 1.269566 0.02525014 MAMDC4 MAM domain containing 4 1.269402 0.03698598 CCDC13 coiled-coil domain containing 13 1.269384 0.04620048 SH2D3A SH2 domain containing 3A 1.26919 0.04955038 ZNF233 zinc finger protein 233 1.269046 0.04749038 ZNF187 zinc finger protein 187 1.269039 0.0497921 1 XP04 exportin 4 1.268991 0.02555127 LIG1 ligase I, DNA, ATP-dependent 1.268785 0.01252088 platelet-activating factor acetylhydrolase lb, PAFAH1B3 catalytic subunit 3 (29kDa) 1.268768 0.02361777 BRD9 bromodomain containing 9 1.268707 0.03008722 NLRC4 NLR family, CARD domain containing 4 1.268671 0.04980405 PAK1IP1 PAK1 interacting protein 1 1.26866 0.0392548 ARMCX4 Armadillo repeat containing, X-linked 4 1.268576 0.04715846 C9orf96 chromosome 9 open reading frame 96 1.268235 0.04998496 protein tyrosine phosphatase, non-receptor PTPN3 type 3 1.268219 0.00406255 GPR87 G protein-coupled receptor 87 1.268184 0.0186203 EFNA3 ephrin-A3 1.268123 0.00940622 discs, large (Drosophila) homolog-associated DLGAP1 protein 1 1.268032 0.02595138 WDFY4 WDFY family member 4 1.267986 0.03854549 PF4 platelet factor 4 1.267797 0.00548331 ERC2 ELKS/RAB6-interacting/CAST family 1.267697 0.00443263 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value member 2 PRP38 pre-mRNA processing factor 38 PRPF38A (yeast) domain containing A 1.267458 0.0372219 phosphoinositide-3 -kinase, catalytic, delta P1K3CD polypeptide 1.267128 0.03911769 C19orf34 chromosome 19 open reading frame 34 1.266845 0.00685461 ITFG1 integrin alpha FG-GAP repeat containing 1 1.266819 0.01601937 Olfactory receptor, family 8, subfamily B, OR8B12 member 1 1.266802 0.04584406 Olfactory receptor, family 5, subfamily K, OR5K2 member 2 1.266728 0.02286792 ANK3 ankyrin 3, node of Ranvier (ankyrin G) 1.266635 0.00897063 NXF4 nuclear RNA export factor 4 pseudogene 1.266614 0.04825277 TRAF1 TNF receptor-associated factor 1 1.266585 0.00887076 ANKH ankylosis, progressive homolog (mouse) 1.266464 0.01 161282 xylosylprotein beta 1,4-galactosyltransferase, B4GALT7 polypeptide 7 (galactosyltransferase I) 1.266262 0.03999451 FBX025 F-box protein 25 1.26606 0.00840386 TMX2 thioredoxin-related transmembrane protein 2 1.266034 0.04371312 C6orfl36 chromosome 6 open reading frame 136 1.265831 0.04085107 IGK@ immunoglobulin kappa locus 1.265694 0.03342056 C15orf42 chromosome 15 open reading frame 42 1.265572 0.00284937 TBCD tubulin folding cofactor D 1.265504 0.04275692 MRPL37 mitochondrial ribosomal protein L37 1.265484 0.03009753 excision repair cross-complementing rodent repair deficiency, complementation group 1 ERCC1 (includes overlapping antisense sequence) 1.265089 0.0424201 1 FLT4 fms-related tyrosine kinase 4 1.265003 0.03423229 TRIM5 tripartite motif-containing 5 1.264801 0.02508482 REG1P regenerating islet-derived 1 pseudogene 1.264619 0.00304221 NCRNAOOIO 5 non-protein coding RNA 105 1.264585 0.03283363 NCOR1 nuclear receptor co-repressor 1 1.264318 0.04431849 TGFBR3 transforming growth factor, beta receptor III 1.264265 0.00830997 leucine-rich repeats and death domain LRDD containing 1.26396 0.04144039 KRTAP17-1 keratin associated protein 17-1 1.26364 0.02127454 SLC26A8 Solute carrier family 26, member 8 1.263636 0.00328375 KIAA1 199 KIAA1 199 1.263474 0.00299676 GOLGA1 golgin A l 1.263419 0.01217355 bromodomain and WD repeat domain BRWD3 containing 3 1.263346 0.00890564 TBRG1 transforming growth factor beta regulator 1 1.263335 0.04770941 SURF1 surfeit 1 1.263306 0.03347953 CD6 CD6 molecule 1.263225 0.03078951 KLHL2 kelch-like 2, Mayven (Drosophila) 1.263015 0.04091952 TRAJ17 T cell receptor alpha joining 17 1.263008 0.03624336 PLK3 polo-like kinase 3 (Drosophila) 1.262955 0.03572863 SST somatostatin 1.262923 0.04839899 SFXN1 sideroflexin 1 1.262718 0.02940824 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCD3 d, member 3 1.26252 0.03847378 SEZ6L Seizure related 6 homolog (mouse)-like 1.262417 0.03785276 Cllorf45 chromosome 11 open reading frame 45 1.262314 0.04663807 ATPase, H+ transporting, lysosomal 38kDa, ATP6V0D2 V0 subunit d2 1.262176 0.04861804 DTNB dystrobrevin, beta 1.262109 0.03182453 SLIT2 slit homolog 2 (Drosophila) 1.261927 0.03785233 DEFA3 defensin, alpha 3, neutrophil-specific 1.261861 0.00224643 CDH16 cadherin 16, KSP-cadherin 1.261774 0.04225288 OXCT1 3-oxoacid CoA transferase 1 1.261625 0.02520766 RILPL2 Rab interacting lysosomal protein-like 2 1.261574 0.04999934 squamous cell carcinoma antigen recognized SART3 by T cells 3 1.261361 0.02103018 NIMA (never in mitosis gene a)- related NEK1 1 kinase 11 1.261331 0.00276633 ASB3 ankyrin repeat and SOCS box-containing 3 1.260703 0.01934422 AASS aminoadipate-semialdehyde synthase 1.260648 0.0152571 DCDC5 doublecortin domain containing 5 1.260575 0.03489532 leukocyte immunoglobulin-like receptor LILRP2 pseudogene 2 1.26038 0.02068243 LAP3 leucine aminopeptidase 3 1.260347 0.04343932 CCDC81 coiled-coil domain containing 8 1 1.260205 0.02935852 HPX hemopexin 1.26013 0.03974206 LCT lactase 1.2601 11 0.04553083 inhibitor of DNA binding 1, dominant ID1 negative helix-loop-helix protein 1.259904 0.02807979 protein phosphatase 2, regulatory subunit A, PPP2R1A alpha 1.25989 0.02451023 FLT3LG fms-related tyrosine kinase 3 ligand 1.259681 0.02655841 solute carrier organic anion transporter SLC01C1 family, member 1C1 1.259636 0.01324903 SBN02 strawberry notch homolog 2 (Drosophila) 1.259623 0.00161167 DENND4A DENN/MADD domain containing 4A 1.259615 0.01542732 FBX04 F-box protein 4 1.259492 0.0287693 MYOIA myosin IA 1.259388 0.02597957 AGXT2L2 alanine-glyoxylate aminotransferase 2-like 2 1.259298 0.02693991 C3orf58 chromosome 3 open reading frame 58 1.259091 0.04608467 MAGEA3 melanoma antigen family A, 3 1.259048 0.00534565 ABHD5 abhydrolase domain containing 5 1.259035 0.00596344 AU RNA binding protein/enoyl-CoA AUH hydratase 1.259026 0.00182977 ATPase, Ca++ transporting, cardiac muscle, ATP2A1 fast twitch 1 1.258936 0.03883481 HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.258927 0.00915241 Cllorf65 chromosome 11 open reading frame 65 1.258777 0.03677547 sema domain, transmembrane domain (TM), SEMA6D and cytoplasmic domain, (semaphorin) 6D 1.258565 0.01420403 RARRES1 retinoic acid receptor responder (tazarotene 1.258483 0.04067531 DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value induced) 1 WSCD1 WSC domain containing 1 1.258403 0.00833534 PDE8A phosphodiesterase 8A 1.258003 0.01337859 FLJ46020 FLJ46020 protein 1.257828 0.04452509 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 2 (GalNAc- GALNT2 T2) 1.257702 0.02625265 P antigen family, member 5 (prostate PAGE5 associated) 1.257566 0.01814344 ARSE arylsulfatase E (chondrodysplasia punctata 1) 1.257193 0.04391929 ELN elastin 1.257191 0.01340862 RBKS ribokinase 1.256993 0.0264602 signal transducer and activator of STAT4 transcription 4 1.25671 0.03391 138 NLRP8 NLR family, pyrin domain containing 8 1.256625 0.01782726 DEAD/H (Asp-Glu-Ala-Asp/His) box DDX26B polypeptide 26B 1.256569 0.03026909 RADIL Ras association and DIL domains 1.256547 0.04544739 NT5C1A 5'-nucleotidase, cytosolic IA 1.256494 0.03504009 CUGBP1 CUG triplet repeat, RNA binding protein 1 1.256281 0.01282044 SVIL supervillin 1.256071 0.02925793 COL25A1 collagen, type XXV, alpha 1 1.256013 0.02472257 QSOX1 quiescin Q6 sulfhydryl oxidase 1 1.255929 0.04328222 RPL13AP3 N/A 1.255772 0.04531485 reversion-inducing-cysteine-rich protein with RECK kazal motifs 1.255739 0.03604279 KIFC2 kinesin family member C2 1.25571 0.03033769 WDR21A WD repeat domain 2 A 1.255693 0.03791939 WD repeat domain, phosphoinositide WIPI1 interacting 1 1.255604 0.01893768 TP53TG3 // LOC729355 N/A 1.255549 0.0020767 Olfactory receptor, family 5, subfamily A, OR5A2 member 2 1.255506 0.01179942 Protein tyrosine phosphatase, non-receptor PTPN20B type 20B 1.255418 0.00627889 DDIT4 DNA-damage-inducible transcript 4 1.255402 0.025832 potassium voltage-gated channel, subfamily H KCNH7 (eag-related), member 7 1.255352 0.02113436 NPFFR2 neuropeptide FF receptor 2 1.255223 0.04185481 potassium voltage-gated channel, shaker- KCNAB1 related subfamily, beta member 1 1.254744 0.01451986 MYOF myoferlin 1.254717 0.00140488 KIF21A kinesin family member 2 1A 1.254658 0.04178249 BST2 bone marrow stromal cell antigen 2 1.254582 0.04913527 ANKRD6 ankyrin repeat domain 6 1.254334 0.03832837 NPTN neuroplastin 1.25423 0.03097989 TMC06 transmembrane and coiled-coil domains 6 1.25402 0.02030981 C6orfl70 chromosome 6 open reading frame 170 1.253451 0.02398408 l / 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value C5orfl7 Chromosome 5 open reading frame 17 1.253056 0.04253337 C10orfl l 9 chromosome 10 open reading frame 19 1.25289 0.02257121 TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, TAF1L 210kDa-like 1.252848 0.00267541 DLX1 Distal-less homeobox 1 1.252657 0.02709251 CATSPERB cation channel, sperm-associated, beta 1.252615 0.02413714 ATP-binding cassette, sub-family C ABCC11 (CFTR/MRP), member 11 1.252585 0.03516509 sodium channel, voltage-gated, type I, alpha SCN1A subunit 1.252542 0.03944445 cystatin 8 (cystatin-related epididymal CST8 specific) 1.252505 0.0416996 CD 109 CD 109 molecule 1.252274 0.03737299 UNQ6484 N/A 1.252122 0.04830452 PCDH20 Protocadherin 20 1.251784 0.04956578 PHF17 PHD finger protein 7 1.25171 0.00222868 missing oocyte, meiosis regulator, homolog MIOS (Drosophila) 1.25141 0.01816732 MFN1 mitofusin 1 1.251298 0.03838396 ZNF615 zinc finger protein 615 1.251296 0.00735893 solute carrier family 29 (nucleoside SLC29A3 transporters), member 3 1.251202 0.04813668 NELL1 NEL-like 1 (chicken) 1.251 108 0.03206594 RBM8A RNA binding motif protein 8A 1.250975 0.00571058 ZNF34 Zinc finger protein 34 1.250962 0.04253855 CRABP2 cellular retinoic acid binding protein 2 1.250729 0.02425808 TMEM1 16 transmembrane protein 116 1.250651 0.02323204 TMEM19 transmembrane protein 19 1.250607 0.02521007 HSDL2 hydroxysteroid dehydrogenase like 2 1.250353 0.0421 1176 CLDN9 claudin 9 1.25029 0.03369131 HYOU1 hypoxia up-regulated 1 1.250242 0.04870764 TBC1D19 TBC1 domain family, member 19 1.250161 0.0243851 1 FOXR1 forkhead box R l 1.25001 1 0.03306343 TM6SF2 transmembrane 6 superfamily member 2 1.249824 0.04033987 BEST3 bestrophin 3 1.249729 0.04319492 polymerase (RNA) III (DNA directed) POLR3E polypeptide E (80kD) 1.249658 0.02249824 Sodium channel, voltage-gated, type VII, SCN7A alpha 1.249531 0.01527615 nudix (nucleoside diphosphate linked moiety NUDT21 X)-type motif 2 1 1.249476 0.04665571 COL4A4 collagen, type IV, alpha 4 1.249356 0.00608043 NPAS3 neuronal PAS domain protein 3 1.249345 0.03665376 cell adhesion molecule with homology to CHLl LICAM (close homolog of LI) 1.249314 0.04459813 MTMR4 myotubularin related protein 4 1.249254 0.03144312 MYOZ2 myozenin 2 1.249074 0.00446696 IER2 immediate early response 2 1.248976 0.02301345 YRDC yrdC domain containing (E. coli) 1.248842 0.03258699 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value C10orf79 chromosome 10 open reading frame 79 1.248821 0.00924585 PSEN1 presenilin 1 1.24867 0.03671699 C5 complement component 5 1.248575 0.02374031 ACCN4 amiloride-sensitive cation channel 4, pituitary 1.248535 0.03166102 AKAP10 A kinase (PRKA) anchor protein 10 1.248322 0.0276429 PER3 period homolog 3 (Drosophila) 1.247536 0.03416167 CYTSA cytospin A 1.247512 0.01152395 5-hydroxytryptamine (serotonin) receptor 3, HTR3E family member E 1.247383 0.04654415 TGDS TDP-glucose 4,6-dehydratase 1.247366 0.03307131 RPLPO ribosomal protein, large, P0 1.247362 0.01263738 CDH7 cadherin 7, type 2 1.247353 0.02363331 S1 3 homolog B, transcription regulator SIN3B (yeast) 1.247232 0.0053172 ATP10D ATPase, class V, type 10D 1.247 81 0.00263839 MED22 mediator complex subunit 22 1.24695 0.02500488 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated MLLT6 to, 6 1.246925 0.02638247 general transcription factor IIIC, polypeptide GTF3C5 5, 63kDa 1.246715 0.02038165 LAMA1 Laminin, alpha 1 1.246648 0.03326858 EXOSC2 exosome component 2 1.246267 0.04580224 KIAA1524 KIAA1524 1.24618 0.02323518 EMP3 epithelial membrane protein 3 1.246123 0.04739262 ACTR8 ARP8 actin-related protein 8 homolog (yeast) .245862 0.04051028 PTPRA protein tyrosine phosphatase, receptor type, A 1.24583 0.00032856 C9or 7 Chromosome 9 open reading frame 97 1.245606 0.04273148 LRRC56 leucine rich repeat containing 56 1.245 143 0.02420723 StAR-related lipid transfer (START) domain STARD8 containing 8 1.244687 0.01282923 ZNF417 Zinc finger protein 417 1.2445 19 0.01805726 cytochrome P450, family 11, subfamily B, CYP11B2 polypeptide 2 1.244442 0.00970924 C17orfl01 chromosome 17 open reading frame 101 1.244439 0.00858935 KHSRP KH-type splicing regulatory protein 1.2444 9 0.018 SCGB1C1 secretoglobin, family 1C, member 1 1.244323 0.01092525 TMEM1 17 transmembrane protein 117 1.24 16 0.02746787 UBA7 ubiquitin-like modifier activating enzyme 7 1.243926 0.04828025 GYG2 glycogenin 2 1.24376 0.03227631 MYBPH myosin binding protein H 1.243 565 0.00017673 ILF3 interleukin enhancer binding factor 3, 90kDa 1.243423 0.02255549 RI S Rho GTPase-activating protein 1.243378 0.03389494 SIGLEC10 sialic acid binding Ig-like lectin 10 1.243329 0.00809374 STRN4 striatin, calmodulin binding protein 4 .243233 0.02055198 sodium channel, voltage-gated, type IX, alpha SCN9A subunit 1.243131 0.00576424 MDFIC MyoD family inhibitor domain containing .242969 0.03261241 NPHP1 nephronophthisis 1 (juvenile) 1.242624 0.0094737 BAIAP2L2 BAI1 -associated protein 2-like 2 1.242568 0.02808724 DB1/ 694 37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value RTTN rotatin 1.242297 0.03280613 R F26 ring finger protein 26 1.242143 0.04297931 GYLTL1B glycosyltransferase-like IB 1.241949 0.03596241 PEX19 peroxisomal biogenesis factor 1 1.241849 0.03167719 MYLK2 myosin light chain kinase 2 1.241836 0.03570873 PRDM11 PR domain containing 11 1.241577 0.027784 SLC44A5 solute carrier family 44, member 5 1.241513 0.02358223 POLR1A polymerase (RNA) I polypeptide A, 194kDa 1.241458 0.0372547 NFASC neurofascin homolog (chicken) 1.241441 0.04145633 KIAA1609 KIAA1609 1.24138 0.02715623 CNTN4 Contactin 4 1.241357 0.04543522 PQLC2 PQ loop repeat containing 2 1.241309 0.01358148 CCDC83 coiled-coil domain containing 83 1.24103 0.04831954 MFAP5 microfibrillar associated protein 5 1.240745 0.04278633 NEURL4 neuralized homolog 4 (Drosophila) 1.240582 0.00550729 5-hydroxytryptamine (serotonin) receptor 7 HTR7 (adenylate cyclase-coupled) 1.239826 0.00939692 AICF APOBEC1 complementation factor 1.239591 0.00588546 family with sequence similarity 114, member FAM1 14A1 Al 1.239459 0.01022173 FOXL2 forkhead box L2 1.239076 0.01996097 TRIM39 tripartite motif-containing 39 1.239033 0.02655088 AMDHD1 amidohydrolase domain containing 1 1.238857 0.0060976 CLSTN3 calsyntenin 3 1.238825 0.02663447 CRIPT cysteine-rich PDZ-binding protein 1.238761 0.0415393 SERHL Serine hydrolase-like 1.238545 0.03856226 INHBB inhibin, beta B 1.238504 0.00822597 SAMD3 sterile alpha motif domain containing 3 1.238401 0.01760916 YAF2 YY1 associated factor 2 1.238376 0.03121256 HERC3 hect domain and RLD 3 1.238202 0.01 12952 IL1F7 interleukin 1 family, member 7 (zeta) 1.238071 0.03715499 SFTPD surfactant protein D 1.238055 0.02607706 UTP18, small subunit (SSU) processome UTP18 component, homolog (yeast) 1.23789 0.01561913 serine peptidase inhibitor-like, with Kunitz SPINLW1 and WAP domains 1 (eppin) 1.237717 0.03300332 TPH2 tryptophan hydroxylase 2 1.237646 0.04347964 SNX8 sorting nexin 8 1.237644 0.0299587 CCNK cyclin K 1.237567 0.03657386 CYTH4 cytohesin 4 1.237449 0.04776589 TEAD4 TEA domain family member 4 1.237242 0.03223393 HKDC1 Hexokinase domain containing 1 1.237239 0.014991 ZBTB32 zinc finger and BTB domain containing 32 1.237223 0.00738703 LRRC25 leucine rich repeat containing 25 1.237094 0.0317678 ADCY10 adenylate cyclase 10 (soluble) 1.23699 0.02988935 MBD3L2 Methyl-CpG binding domain protein 3-like 2 1.236936 0.03597342 CCDC110 coiled-coil domain containing 110 1.236882 0.03089214 NCRNA0016 1 non-protein coding RNA 161 1.236863 0.04879846 CYP11A1 cytochrome P450, family 11, subfamily A, 1.236533 0.0107929 )B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value polypeptide 1 FAAH2 fatty acid amide hydrolase 2 1.236528 0.0427251 SYMPK symplekin 1.236523 0.00753091 NLRP14 NLR family, pyrin domain containing 14 1.235995 0.02067863 SPATA13 spermatogenesis associated 13 1.235982 0.01841387 FLJ14100 hypothetical protein FLJ14100 1.235981 0.01346477 BMS1P5 BMS1 pseudogene 5 1.235944 0.02398758 ZNF428 zinc finger protein 428 1.235923 0.02032021 GALNAC4S- 6ST B cell RAG associated protein 1.235856 0.00316015 TNRC6A trinucleotide repeat containing 6A 1.235851 0.04134624 nuclear receptor subfamily 2, group F, NR2F1 member 1 1.235843 0.04550788 TMC3 transmembrane channel-like 3 1.235688 0.00186255 IL4R interleukin 4 receptor 1.235665 0.0349981 ribonuclease L (2',5'-oligoisoadenylate RNASEL synthetase-dependent) 1.235518 0.02035331 PRELID2 PRELI domain containing 2 1.235512 0.04554335 PCNX pecanex homolog (Drosophila) 1.235013 0.04108437 ZNF79 zinc finger protein 79 1.235001 0.04024746 PLXNA1 plexin A l 1.234965 0.04264428 METTL13 methyltransferase like 13 1.234935 0.01797137 CGN cingulin 1.234766 0.04962725 BTB and CNC homology , basic leucine BACH1 zipper transcription factor 1 1.234722 0.01598341 GADL1 glutamate decarboxylase-like 1 1.234581 0.03999796 G protein-coupled receptor, family C, group GPRC6A 6, member A 1.234368 0.03671451 OTX1 orthodenticle homeobox 1 1.234312 0.03872799 adaptor-related protein complex , sigma 2 AP1S2 subunit 1.234244 0.04050856 Clorfl62 chromosome 1 open reading frame 162 1.233765 0.04205373 GIMAP8 GTPase, IMAP family member 8 1.233485 0.04245494 PRKCE protein kinase C, epsilon 1.233257 0.02306676 aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 2; bile acid binding protein; 3-alpha hydroxysteroid AKR1C2 dehydrogenase, type III) 1.232654 0.03067469 upper zone of growth plate and cartilage UCMA matrix associated 1.232605 0.0148044 FLJ26850 FLJ26850 protein 1.232564 0.00472674 PTDSS2 phosphatidylserine synthase 2 1.232397 0.0121 1942 LAPTM5 lysosomal protein transmembrane 5 1.232132 0.04167828 E2F8 E2F transcription factor 8 1.232086 0.00048585 AMY1A amylase, alpha 1A (salivary) 1.231974 0.03097984 BBS9 Bardet-Biedl syndrome 9 1.231838 0.04666133 butyrobetaine (gamma), 2-oxoglutarate dioxygenase (gamma-butyrobetaine BBOX1 hydroxylase) 1 1.231478 0.01092679 SERHL2 serine hydrolase-like 2 1.231232 0.02799732 DB1/ 69437 5 16. 1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value SERAC1 serine active site containing 1 1.23 11 2 0.04286629 TROAP trophinin associated protein (tastin) 1.23 1035 0.03471954 DUS3L dihydrouridine synthase 3-like (S. cerevisiae) 1.230713 0.01696831 Ganglioside-induced differentiation- GDAP1L1 associated protein 1-like 1 1.230631 0.01765892 solute carrier family 25 (mitochondrial SLC25A23 carrier; phosphate carrier), member 23 1.230625 0.02786495 PDI 1L PDLIM1 interacting kinase 1 like 1.230556 0.01222398 OTOR otoraplin 1.230331 0.0006035 UPF3 regulator of nonsense transcripts UPF3A homolog A (yeast) 1.23028 0.0287505 solute carrier family 25 (mitochondrial SLC25A12 carrier, Aralar), member 12 1.230237 0.014549 LSM7 homolog, U6 small nuclear RNA LSM7 associated (S. cerevisiae) 1.230163 0.02583374 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), LILRB2 member 2 1.229932 0.03151425 DnaJ (Hsp40) homolog, subfamily C, member DNAJC10 10 1.229817 0.03064105 RASGEF1A RasGEF domain family, member 1A 1.229 6 0.0460017 ZNF679 zinc finger protein 679 1.229125 0.04788786 cholinergic receptor, nicotinic, alpha 1 CHRNAl (muscle) 1.229101 0.01837677 DPYSL5 dihydropyrimidinase-like 5 1.22903 1 0.01631308 FCHSD1 FCH and double SH3 domains 1 1.229024 0.02041655 NKIRAS1 NFKB inhibitor interacting Ras-like 1 1.228784 0.01403705 steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase SRD5A2 alpha 2) 1.228617 0.01614202 mannosyl (alpha- ,6-)-glycoprotein beta- 1,6- MGAT5B N-acetyl-glucosaminyltransferase, isozyme B 1.228543 0.00058875 GK 1 gastrokine 1 1.228174 0.00324149 Cas-Br-M (murine) ecotropic retroviral CBLC transforming sequence c .228 113 0.0475787 CXorf50B N/A 1.227824 0.00097768 LRRC36 leucine rich repeat containing 36 1.227789 0.04154441 UTS2D urotensin 2 domain containing 1.227373 0.02920385 OPN5 opsin 5 1.227325 0.0068055 PCDHB10 protocadherin beta 10 1.227223 0.04429794 ArfGAP with coiled-coil, ankyrin repeat and ACAP2 PH domains 2 1.227105 0.03728326 CAP, adenylate cyclase-associated protein, 2 CAP2 (yeast) 1.226974 0.04016996 FHIT fragile histidine triad gene .226757 0.04422508 C2CD2 C2 calcium-dependent domain containing 2 1.226726 0.00134391 R3HDM2 R3H domain containing 2 1.22664 1 0.01355409 AHCYL1 adenosylhomocysteinase-like 1 1.226394 0.00961029 CCL21 chemokine (C-C motif) ligand 2 1 1.22634 1 0.00087255 MCM10 minichromosome maintenance complex 1.226335 0.03173039 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value component 10 myosin, light chain 3, alkali; ventricular, MYL3 skeletal, slow 1.226334 0.04743267 ZNF14 zinc finger protein 14 1.226214 0.00392558 FLJ44635 TPTl-like protein 1.226008 0.04428207 FOXD3 forkhead box D3 1.226 0.04097072 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCA1 a, member 1 1.225814 0.02792728 GLTP glycolipid transfer protein 1.225619 0.02234763 v-crk sarcoma virus CT10 oncogene homolog CRKL (avian)-like 1.22546 0.02004339 FBXL F-box and leucine-rich repeat protein 1 1.225415 0.02509421 TRAF5 T F receptor-associated factor 5 1.225339 0.00872158 HOXD1 homeobox Dl 1 1.225316 0.006661 15 RAD51L1 RAD51-like 1 (S. cerevisiae) 1.225063 0.03158881 kelch repeat and BTB (POZ) domain KBTBD3 containing 3 1.225048 0.00868803 LUZP4 leucine zipper protein 4 1.225036 0.0153911 1 DEAH (Asp-Glu-Ala-His) box polypeptide DHX34 34 1.224813 0.03617669 CNPY2 canopy 2 homolog (zebrafish) 1.224602 0.04495685 PRP39 pre-mRNA processing factor 39 PRPF39 homolog (S. cerevisiae) 1.22453 0.01035303 ASGR2 asialoglycoprotein receptor 2 1.224014 0.0055253 PRKG1 protein kinase, cGMP-dependent, type I 1.223879 0.04519305 disabled homolog 2, mitogen-responsive DAB2 phosphoprotein (Drosophila) 1.223839 0.00800414 olfactory receptor, family 5, subfamily H, OR5H1 member 1 1.223542 0.0050431 SRPK2 SFRS protein kinase 2 1.22325 0.01501723 small nuclear ribonucleoprotein 35kDa SNR P35 (U1 1/U12) 1.222875 0.00777022 Olfactory receptor, family 2, subfamily M, OR2M7 member 7 1.222822 0.03207624 TCOF1 Treacher Collins-Franceschetti syndrome 1 1.222738 0.00826843 ANK2 ankyrin 2, neuronal 1.222676 0.00634497 G2E3 G2/M-phase specific E3 ubiquitin ligase 1.222631 0.00185943 solute carrier family 39 (zinc transporter), SLC39A6 member 6 1.22186 0.0061314 ZNF425 Zinc finger protein 425 1.221839 0.03781226 POPDC2 popeye domain containing 2 1.221836 0.00725864 KCNE1L KCNEl-like 1.221821 0.01817093 TSC22D2 TSC22 domain family, member 2 1.221814 0.022301 excision repair cross-complementing rodent ERCC6 repair deficiency, complementation group 6 1.221669 0.02154465 solute carrier family 1 (glutamate transporter), SLC1A7 member 7 1.221415 0.03713144 ATP-binding cassette, sub-family A (ABCl), ABCA10 member 10 1.220669 0.00882892 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value pantothenate kinase 1 1.220656 0.01608154 solute carrier family 12 (potassium/chloride transporters), member 9 1.22038 0.04903245 transmembrane protein 156 1.220203 0.03900463 Ca++-dependent secretion activator 1.219984 0.04382195 SPARC-like 1 (hevin) 1.219852 0.03913905 Sorbin and SH3 domain containing 1 1.219499 0.01097803 tubulin folding cofactor C 1.219283 0.02493064 hyaluronan and proteoglycan link protein 1 1.219148 0.02616776 forkhead box D4 1.219085 0.02737425 COMM domain containing 9 1.218971 0.03277739 lymphocyte antigen 9 1.218677 0.04751694 lysyl oxidase-like 3 1.218312 0.02203561 tudor domain containing 9 1.218186 0.0036461 Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog 1.218069 0.00514118 mucin 13, cell surface associated 1.218026 0.01253442 F-box and leucine-rich repeat protein 13 1.217916 0.00963049 zinc finger, DHHC-type containing 15 1.217781 0.00404771 kinesin family member 2B 1.217704 0.0006307 melanoma antigen family D, 4 1.217564 0.02132055 microsomal triglyceride transfer protein 1.217075 0.04306468 chromosome 1 open reading frame 109 1.216927 0.03071822 N-acylaminoacyl-peptide hydrolase 1.21679 0.04407907 THO complex 4 1.216787 0.0403008 MMS19 nucleotide excision repair homolog (S. cerevisiae) 1.216589 0.03922461 receptor (TNFRSF)-interacting serine- threonine kinase 1 1.216346 0.01773695 MCF.2 cell line derived transforming sequence-like 2 1.216222 0.03044115 neogenin homolog 1 (chicken) 1.216163 0.03251328 Hypothetical LOC442092 1.215765 0.01544065 centrosomal protein 1lOkDa 1.215556 0.03730905 potassium voltage-gated channel, KQT-like subfamily, member 3 1.215354 0.03121697 oxoeicosanoid (OXE) receptor 1 1.215246 0.02868055 forkhead box J2 1.214929 0.04716483 tripartite motif-containing 31 1.214792 0.04103994 proteasome (prosome, macropain) 26S subunit, non-ATPase, 13 1.214569 0.00673002 Solute carrier family 35, member E2 1.214523 0.03901927 alcohol dehydrogenase IB (class I), beta polypeptide 1.214395 0.00100821 Microtubule associated serine/threonine kinase family member 4 1.214111 0.0028083 fibrous sheath interacting protein 1 1.213903 0.04737353 zinc finger CCCH-type containing 14 1.213594 0.01712715 xin actin-binding repeat containing 2 1.213568 0.03649298 dynein, axonemal, heavy chain 8 1.213317 0.01764265 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value sortilin-related VPS 10 domain containing SORCS1 receptor 1 1.213159 0.03788062 RAS guanyl releasing protein 2 (calcium and RASGRP2 DAG-regulated) 1.21309 0.01101469 vacuolar protein sorting 13 homolog C (S. VPS13C cerevisiae) 1.213066 0.03233575 GSDMB gasdermin B 1.212917 0.02996031 carbamoyl-phosphate synthase 1, CPS1 mitochondrial 1.21283 0.04907995 FLJ10404 Hypothetical protein FLJ 10404 1.212673 0.00191574 PHF16 PHD finger protein 16 1.212564 0.01756385 C8orf78 chromosome 8 open reading frame 78 1.212201 0.02255807 MEP1A meprin A, alpha (PABA peptide hydrolase) 1.211724 0.04853678 ADCY1 adenylate cyclase 1 (brain) 1.211412 0.02100712 TSPAN12 tetraspanin 12 1.211375 0.02651059 potassium voltage-gated channel, KQT-like CNQ4 subfamily, member 4 1.211356 0.0320885 ATPase, H+ transporting, lysosomal ATP6V1H 50/57kDa, V I subunit 1.21 1331 0.026815 caspase 8, apoptosis-related cysteine CASP8 peptidase 1.211198 0.01464514 RNF141 ring finger protein 141 1.211196 0.02991816 ectonucleotide ENPP2 pyrophosphatase/phosphodiesterase 2 1.211 162 0.0425432 HINT1 histidine triad nucleotide binding protein 1 1.210712 0.04891515 C8orfl7 chromosome 8 open reading frame 17 1.210297 0.04478836 sphingomyelin phosphodiesterase 3, neutral SMPD3 membrane (neutral sphingomyelinase II) 1.210189 0.04469751 COL6A2 collagen, type VI, alpha 2 1.210041 0.0485979 ZAN zonadhesin 1.209973 0.039782 transmembrane (C-terminal) protease, serine TMPRSS12 12 1.209923 0.00684086 CALN1 calneuron 1 1.209429 0.03581015 RAGE renal tumor antigen 1.209223 0.0471772 FOLR1 folate receptor 1 (adult) 1.209123 0.04577546 PCSK9 Proprotein convertase subtilisin/kexin type 9 1.209005 0.00561032 LZTFL1 leucine zipper transcription factor-like 1 1.208827 0.03900355 FLJ41327 FLJ4 1327 protein 1.208808 0.01584038 protein phosphatase, EF-hand calcium PPEF1 binding domain 1 1.208483 0.00013434 MAPK1 mitogen-activated protein kinase 1 1.208451 0.02953756 X-ray repair complementing defective repair XRCC2 in Chinese hamster cells 2 1.208432 0.04292725 SCNN1D sodium channel, nonvoltage-gated 1, delta 1.208383 0.02079827 CEP250 centrosomal protein 250kDa 1.208013 0.0236764 OPTN Optineurin 1.207919 0.00521899 PCTK2 PCTAIRE protein kinase 2 1.207796 0.02335376 ZNF619 zinc finger protein 619 1.207776 0.04679568 OSBP2 oxysterol binding protein 2 1.207761 0.01456842 CCDC84 coiled-coil domain containing 84 1.207745 0.03929433 >B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value GPR112 G protein-coupled receptor 112 1.207628 0.00260127 RRAGC Ras-related GTP binding C 1.207521 0.03659237 KLK8 kallikrein-related peptidase 8 1.207414 0.01697536 GYS1 glycogen synthase 1 (muscle) 1.207255 0.0073425 RTN1 reticulon 1 1.207216 0.0192233 PAK3 p 1 protein (Cdc42/Rac)-activated kinase 3 1.207161 0.04030197 obscurin, cytoskeletal calmodulin and titin- OBSCN interacting RhoGEF 1.206772 0.02149618 TEX28 testis expressed 28 1.206549 0.04484958 ANKRD29 ankyrin repeat domain 29 1.206277 0.02225841 phosphatidylinositol transfer protein, PITPNM1 membrane-associated 1 1.20625 0.04758375 X , Kell blood group complex subunit- XKR3 related family, member 3 1.205822 0.04528149 ZNF528 zinc finger protein 5 1.205598 0.02553913 doublesex and mab-3 related transcription DMRT2 factor 2 1.205569 0.01802004 ME B meprin A, beta 1.205569 0.001 13685 SH3-domain GRB2-like (endophilin) SGIP1 interacting protein 1 1.205394 0.03094877 IGSF9 immunoglobulin superfamily, member 9 1.205277 0.0238431 1 IGH@ immunoglobulin heavy locus 1.205258 0.01282709 TBL2 transducin (beta)-like 2 1.205045 0.04332468 general transcription factor IIH, polypeptide GTF2H3 3, 34kDa 1.204669 0.0151408 MCOLN3 mucolipin 3 1.204651 0.00181367 minichromosome maintenance complex MCM3 component 3 1.204643 0.02501993 TRIM16 tripartite motif-containing 16 1.204583 0.02110382 RHOBTB1 Rho-related BTB domain containing 1 1.204574 0.0231 36 TSNARE1 t-SNARE domain containing 1 1.204487 0.00549102 Caspase 14, apoptosis-related cysteine CASP14 peptidase 1.204455 0.02818916 CDH26 cadherin 26 1.204397 0.01957364 TTLL7 tubulin tyrosine ligase-like family, member 7 1.204374 0.00056749 EDA ectodysplasin A 1.203475 0.04743863 olfactory receptor, family 2, subfamily T, OR2T27 member 27 1.203472 0.01128284 TAF12 RNA polymerase II, TATA box binding protein (TBP)-associated factor, TAF12 20kDa 1.203286 0.02106946 cytochrome P450, family 24, subfamily A, CYP24A1 polypeptide 1 1.202964 0.01758295 GNRH2 gonadotropin-releasing hormone 2 1.202871 0.00455354 transient receptor potential cation channel, TRPC4AP subfamily C, member 4 associated protein 1.202778 0.0247338 Protein phosphatase 2 (formerly 2A), PPP2R3B regulatory subunit B", beta 1.20235 0.0467168 Similar to ubiquitin-conjugating enzyme E2Q FLJ43276 2 1.202268 0.03190402 DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value BTNL3 butyrophilin-like 3 1.202192 0.00231857 RGSL1 regulator of G-protein signaling like 1 1.202077 0.00594699 TPO thyroid peroxidase 1.202069 0.01017159 SCEL sciellin 1.201887 0.00233167 SYNJ2 synaptojanin 2 1.201541 0.01 137583 EHD1 EH-domain containing 1 1.201044 0.0233041 1 ACINI apoptotic chromatin condensation inducer 1 1.201026 0.02887224 IL20 interleukin 20 1.20095 0.03008605 family with sequence similarity 90, member FAM90A1 A l 1.200927 0.00186085 ROD1 regulator of differentiation 1 (S. ROD1 pombe) 1.200754 0.0474292 UDP-GlcNAc:betaGal beta-l,3-N- B3GNT5 acetylglucosaminyltransferase 5 1.200695 0.01960692 cAMP responsive element binding protein 3- CREB3L1 like 1 1.200668 0.01419674 SPON1 spondin 1, extracellular matrix protein 1.200668 0.02924293 DEPDC5 DEP domain containing 5 1.200388 0.04198871 solute carrier family 4, sodium bicarbonate SLC4A7 cotransporter, member 7 1.200374 0.01216306 Excision repair cross-complementing rodent ERCC8 repair deficiency, complementation group 8 1.20021 1 0.01619386 SARI A SARI homolog A (S. cerevisiae) 1.200178 0.02654978 CCHCR1 coiled-coil alpha-helical rod protein 1 1.200107 0.00917738 acyl-CoA dehydrogenase, short/branched ACADSB chain 1.20001 0.02790511 MEIS2 Meis homeobox 2 1.199965 0.02108226 DBF4B DBF4 homolog B (S. cerevisiae) 1.199619 0.03549086 interleukin 2 receptor, gamma (severe IL2RG combined immunodeficiency) 1.199506 0.00788149 CRAMP 1L Crm, cramped-like (Drosophila) 1.199274 0.03778153 CAPN12 Calpain 12 1.199157 0.00757691 KIAA0141 KIAA0141 1.198884 0.03352701 triggering receptor expressed on myeloid TREML1 cells-like 1 1.198054 0.04780684 NINL ninein-like 1.197949 0.02748427 SLC46A2 solute carrier family 46, member 2 1.197672 0.02290017 ALB albumin 1.197399 0.041 1184 transition protein 2 (during histone to TNP2 protamine replacement) 1.19722 0.00193066 RNA binding motif, single stranded RBMS3 interacting protein 3 1.196392 0.03757412 EFCAB5 EF-hand calcium binding domain 5 1.196327 0.00695507 RPH3A rabphilin 3A homolog (mouse) 1.196274 0.03001022 3-Mar N/A 1.196125 0.01527518 ZNF227 zinc finger protein 227 1.19555 0.01396527 Solute carrier family 22 (organic anion/cation SLC22A10 transporter), member 10 1.195396 0.04256239 TUBGCP5 tubulin, gamma complex associated protein 5 1.195396 0.02824091 KIAA0317 KIAA0317 1.195135 0.04304959 DBl/ 69437516.1 Supplemental Table 1 . Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P value SIK1 salt-inducible kinase 1 1.195008 0.0327209 DnaJ (Hsp40) homolog, subfamily B, member DNAJB5 5 1.194948 0.02080713 WDR59 WD repeat domain 59 1.194575 0.02706941 WDR90 WD repeat domain 90 1.194397 0.00265406 MOXD1 monooxygenase, DBH-like 1 1.194103 0.02778465 STAB1 stabilin 1 1.193369 0.03979409 MTMR6 myotubularin related protein 6 1.193367 0.03304742 differentially expressed in FDCP 8 homolog DEF8 (mouse) 1.193266 0.0366666 KRT3 keratin 3 1.19301 0.00261699 C17orf47 chromosome 17 open reading frame 47 1.192946 0.01988324 F13B coagulation factor XIII, B polypeptide 1.192215 0.03738782 protein phosphatase 1, regulatory (inhibitor) PPP1R3A subunit 3A 1.191818 0.04093887 CLIC5 chloride intracellular channel 5 1.191528 0.02173546 ZDHHC8 zinc finger, DHHC-type containing 8 1.191091 0.018042 DCL 1 doublecortin-like kinase 1 1.190858 0.01408673 CLCN4 chloride channel 4 1.190833 0.03606835 SPATS 1 spermatogenesis associated, serine-rich 1 1.189964 0.02817104 FRMD5 FERM domain containing 5 1.18974 0.02059221 eukaryotic translation initiation factor 3, EIF3C subunit C 1.18965 0.03850882 C7orf27 chromosome 7 open reading frame 27 1.189607 0.04936258 family with sequence similarity 178, member FAM178A A 1.189489 0.03542246 UDP glucuronosyltransferase 2 family, UGT2B4 polypeptide B4 1.18914 0.02762916 C22orf31 chromosome 22 open reading frame 31 1.188471 0.04342905 CFHR3 complement factor H-related 3 1.188091 0.01982027 protein phosphatase 2, regulatory subunit B, PPP2R2B beta 1.188035 0.02405195 ITPK1 inositol 1,3,4-triphospliate 5/6 kinase 1.187707 0.02648192 wingless-type MMTV integration site family, W T5A member 5A 1.187286 0.03638738 GSX2 GS homeobox 2 1.187258 0.04749432 FLJ44048 FLJ44048 protein 1.187132 0.02872413 CAPRIN2 caprin family member 2 1.187106 0.0381396 potassium voltage-gated channel, subfamily H KCNH6 (eag-related), member 6 1.186893 0.00325637 IMP (inosine 5'-monophosphate) IMPDH2 dehydrogenase 2 1.186305 0.02984448 FGG fibrinogen gamma chain 1.18591 0.03549757 solute carrier family 27 (fatty acid SLC27A3 transporter), member 3 1.185586 0.02812566 TEX11 testis expressed 11 1.18556 0.02007695 patatin-like phospholipase domain containing PNPLA1 1 1.185535 0.02326484 CDP-diacylglycerol synthase (phosphatidate

C D S 1 cytidylyltransferase) 1 1.184946 0.02636899 n R Q 5 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value Solute carrier family 27 (fatty acid SLC27A6 transporter), member 6 0.03970073 DPYSL2 dihydropyrimidinase-like 2 0.02182736 MCTP1 multiple C2 domains, transmembrane 1 0.03360385 TRIB1 tribbles homolog 1 (Drosophila) 0.02736849 IFI16 interferon, gamma-inducible protein 16 0.0074908 CDH3 cadherin 3, type 1, P-cadherin (placental) 0.01625922 DnaJ (Hsp40) homolog, subfamily C, member DNAJC16 16 0.0261288 DGKG diacylglycerol kinase, gamma 90kDa 0.039706 BPY2 basic charge, Y-linked, 2 0.03254044 ZNF583 zinc finger protein 583 0.02485305 ADAM30 ADAM metallopeptidase domain 30 0.00616206 DTNA dystrobrevin, alpha 0.02930348 CASR calcium-sensing receptor 0.03323074 ZNF345 zinc finger protein 345 0.00924459 ZNF509 Zinc finger protein 509 0.04998016 ZNRF1 zinc and ring finger 1 0.0099705 DPY19L3 dpy-19-like 3 (C. elegans) 0.01666136 ATP13A1 ATPase type 13Al 0.04005452 W K4 WNK lysine deficient protein kinase 4 0.04657409 NPSR1 neuropeptide S receptor 1 0.02172977 ZNF687 zinc finger protein 687 0.02918329 alanyl-tRNA synthetase 2, mitochondrial AARS2 (putative) 1.180396 0.02086541 Golgi autoantigen, golgin subfamily a-like FLJ401 13 pseudogene 1.180388 0.00047194 adaptor-related protein complex 4, beta 1 AP4B1 subunit 0.01384674 KPNA5 karyopherin alpha 5 (importin alpha 6) 0.02793043 IMPG1 interphotoreceptor matrix proteoglycan 1 0.03330314 COL9A1 collagen, type IX, alpha 1 0.02346278 WDR46 WD repeat domain 46 0.01295145 HYI hydroxypyruvate isomerase homolog (E. coli) 0.03586758 Golgi associated, gamma adaptin ear GGA1 containing, ARF binding protein 1 0.01209954 MAB21L2 mab-21-like 2 (C. elegans) 0.01490822 PDZD2 PDZ domain containing 2 0.04742919 KIAA0467 KIAA0467 0.00480777 MY09B myosin IXB 0.00019001 PAX3 paired box 3 0.02956595 NIDI nidogen 1 0.02300942 ALOXE3 Arachidonate lipoxygenase 3 0.04581467 1-acylglycerol-3 -phosphate O-acyltransf erase 4 (lysophosphatidic acid acyltransferase, AGPAT4 delta) 0.00637736 RNF25 Ring finger protein 25 0.02427105 FOXP2 forkhead box P2 0.02296124 PNMAL1 PNMA-like 1 0.04671811 TRPV6 transient receptor potential cation channel, 0.00208195 DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value subfamily V, member 6 ZNF607 zinc finger protein 607 1.17363 0.01986909 DSC3 desmocollin 3 1.173507 0.00852276 Histidine acid phosphatase domain containing HISPPD2A 2A 1.173422 0.04406193 AHNAK AHNAK nucleoprotein 1.173278 0.0004565 pleckstrin homology domain containing, PLEKH02 family O member 2 1.17267 0.01898245 PLCB4 phospholipase C, beta 4 1.172513 0.04330856 C16orf68 chromosome 16 open reading frame 68 1.17127 0.01823989 signal transducer and activator of STAT5A transcription 5A 1.170663 0.01131636 CLEC18A C-type lectin domain family 18, member A 1.17033 0.0455398 intraflagellar transport 52 homolog IFT52 (Chlamydomonas) 1.16959 0.01712765 NOL6 nucleolar protein family 6 (RNA-associated) 1.169534 0.04780299 LON peptidase N-terminal domain and ring LONRF1 finger 1 1.169296 0.03987327 C6orf58 chromosome 6 open reading frame 58 1.168817 0.03032013 NPHP4 nephronophthisis 4 1.168254 0.03145141 GNPAT glyceronephosphate O-acyltransferase 1.167893 0.02519736 KIAA0355 KIAA0355 1.167416 0.01082776 PABPC3 poly(A) binding protein, cytoplasmic 3 1.167305 0.02673658 SPACA3 Sperm acrosome associated 3 1.16728 0.0489063 C20orfl 7 chromosome 20 open reading frame 17 1.167178 0.04091815 PRR18 proline rich 18 1.167034 0.01554887 SEC23A Sec23 homolog A (S. cerevisiae) 1.166758 0.0064721 ZNF783 zinc finger family member 783 1.166506 0.01530829 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) EGFR oncogene homolog, avian) 1.166192 0.04292096 THAP9 THAP domain containing 9 1.166034 0.02042772 folliculogenesis specific basic helix-loop- FIGLA helix 1.165536 0.0486831 KLHDC9 kelch domain containing 9 1.165134 0.0305178 PIWIL2 piwi-like 2 (Drosophila) 1.164572 0.02796603 cleavage and polyadenylation specific factor CPSF7 7, 59kDa 1.164181 0.04438468 HSH2D hematopoietic SH2 domain containing 1.163909 0.02101095 MAN2B1 mannosidase, alpha, class 2B, member 1 1.163671 0.0230003 TMEM40 transmembrane protein 40 1.163525 0.01 127356 Adhesion molecule, interacts with CXADR AMICA1 antigen 1 1.162197 0.03518972 AT 11 N-acetyltransferase 11 1.161757 0.00136992 NOSTRIN nitric oxide synthase trafficker 1.161744 0.04875515 WDR77 WD repeat domain 77 1.161034 0.0464362 SEZ6 Seizure related 6 homolog (mouse) 1.160645 0.00582668 HSFY2 heat shock transcription factor, Y linked 2 1.160551 0.04492153 GMPS guanine monphosphate synthetase 1.160098 0.02920418 PDCD1 1 programmed cell death 11 1.159681 0.03268893 Bl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P Change value KIF27 kinesin family member 27 1.159524 0.00724317 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular FLT1 permeability factor receptor) 1.158691 0.02251696 ESR1 estrogen receptor 1 1.158432 0.04355614 IP013 importin 13 1.158266 0.041 10354 CD1D CD Id molecule 1.157526 0.0488465 C16orf58 chromosome 16 open reading frame 58 1.157353 0.01567337 RXFP2 relaxin/insulin-like family peptide receptor 2 1.157118 0.03208373 POTEG POTE ankyrin domain family, member G 1.15675 0.0279091 ZW10, kinetochore associated, homolog ZW10 (Drosophila) 1.156689 0.04370405 HFM1, ATP-dependent DNA helicase HFM1 homolog (S. cerevisiae) 1.155649 0.01725609 ZNF620 zinc finger protein 620 1.155478 0.01498643 EFCAB7 EF-hand calcium binding domain 7 1.155364 0.04868796 neighbor of BRCA1 gene 2 (non-protein NBR2 coding) 1.154574 0.0342684 translocase of inner mitochondrial membrane TIMM8A 8 homolog A (yeast) 1.154276 0.01892605 GOSR2 golgi SNAP receptor complex member 2 1.154174 0.02083885 HVCN1 hydrogen voltage-gated channel 1 1.153664 0.04150092 integrin, alpha L (antigen CD1 1A (pi 80), lymphocyte function-associated antigen ITGAL alpha polypeptide) 1.153175 0.0121027 TCP10L T-complex 10 (mouse)-like 1.153159 0.02041266 CILP2 cartilage intermediate layer protein 2 1.153042 0.024871 HIST1H4F histone cluster 1, H4f 1.152071 0.0381848 SORBS3 sorbin and SH3 domain containing 3 1.151912 0.0398458 IL22RA1 interleukin 22 receptor, alpha 1 1.151869 0.03723606 PPP4R1 protein phosphatase 4, regulatory subunit 1 1.151406 0.0099078 C3orf35 chromosome 3 open reading frame 3 1.151345 0.01326453 cytochrome P450, family 2, subfamily C, CYP2C18 polypeptide 18 1.151319 0.04873183 FLJ25715 hypothetical protein FLJ25715 1.150845 0.03539013 DGKB diacylglycerol kinase, beta 90kDa 1.150602 0.02125358 AKAP2 A kinase (PRKA) anchor protein 2 1.150537 0.02056527 intraflagellar transport 172 homolog IFT172 (Chlamydomonas) 1.150365 0.02101366

Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CECR6 cat eye syndrome chromosome region, candidate 6 4.533043 0.00120481 THOC5 THO complex 5 4.256919 0.00876836 APPL2 adaptor protein, phosphotyrosine interaction, PH 3.836681 0.04778387 domain and leucine zipper containing 2 PSMG2 proteasome (prosome, macropain) assembly 3.493733 0.03165942

DBl/ 69437516. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value chaperone 2 Clorfl07 chromosome 1 open reading frame 107 3.395923 0.00436079 CHMP7 CHMP family, member 7 3.295925 0.04618667 DOCK1 dedicator of cytokinesis 1 3.213632 0.03198286 MDN1 DN l . midasin homolog (yeast) 3.21 1667 0.02237256 RBM43 #N/A 3.196485 0.00631414 CCNT1 cyclin T l 3.106008 0.0342957 IFT52 intraflagellar transport 52 homolog 3.046151 0.01229609 (Chiamydomonas) ABCA12 ATP-binding cassette, sub-family A (ABC1), 3.02442 0.00623101 member 12 FBX025 F-box protein 25 3.021057 0.00368625 G3BP1 GTPase activating protein (SH3 domain) binding 2.994202 0.01682477 protein 1 ITPR1 inositol 1,4, -triphosphate receptor, type 1 2.988401 0.00625779 MED1 mediator complex subunit 1 2.96932 0.0409564 Clorf54 #N/A 2.955018 0.00026548 ELK1 ELK1, member ofETS oncogene family 2.954365 0.01660971 NUP214 nucleoporin 214kDa 2.948931 0.0326838 INADL InaD-like (Drosophila) 2.899368 0.00507621 HCN4 hyperpolarization activated cyclic nucleotide-gated 2.889932 0.02627041 potassium channel 4 ALKBH5 alkB, alkylation repair homolog 5 (E. coli) 2.85896 0.03354708 DOLK dolichol kinase 2.854543 0.01302542 ATP8B2 ATPase, class I, type 8B, member 2 2.850312 0.04602733 ERRFIl ERBB receptor feedback inhibitor 1 2.848611 0.03785734 CTNNBL catenin, beta like 1 2.847563 0.04508615 1 STIM2 stromal interaction molecule 2 2.835404 0.0459367 TNK2 tyrosine kinase, non-receptor, 2 2.830558 0.03729109 BAX BCL2-associated X protein 2.80332 0.04525024 PI4K2A #N/A 2.796562 0.0050034 FUNDC2 FUN14 domain containing 2 2.773584 0.00524994 MAP3K2 mitogen-activated protein kinase kinase kinase 2 2.768704 0.04766367 N T nicotinamide nucleotide transhydrogenase 2.768045 0.00941208 RAB30 RAB30, member RAS oncogene family 2.747985 0.04482544 CTSA cathepsin A 2.746964 0.03877969 AFF1 AF4/FMR2 family, member 1 2.739383 0.04907813 DDHD2 DDHD domain containing 2 2.735836 0.04539782 NUDT9 nudix (nucleoside diphosphate linked moiety X)- 2.735101 0.00850058 type motif 9 BRAF v-raf murine sarcoma viral oncogene homolog B1 2.734356 0.03364438 THBS3 thrombospondin 3 2.718379 0.02243978 DHX57 DEAH (Asp-Glu-Ala-Asp/His) box polypeptide 2.71681 0.01686649 57 C6orfl68 chromosome 6 open reading frame 168 2.709293 0.02722808 R3HDM2 R3H domain containing 2 2.709092 0.00453719 SMURF1 SMAD specific E3 ubiquitin protein ligase 1 2.701271 0.01558087 UTRN utrophin 2.695947 0.01243512 BRD8 bromodomain containing 8 2.694947 0.00909826 1/ 694375 16.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value IL1RAP interleukin 1 receptor accessory protein 2.694309 0.02831857 NBEA neurobeachin 2.693884 0.02193306 DIAPH1 diaphanous homolog 1 (Drosophila) 2.685718 0.03000495 MKRN1 makorin ring finger protein 1 2.685032 0.00157199 SYT10 Synaptotagmin X 2.65176 0.01295566 DENND5 DENN/MADD domain containing 5A 2.65 1474 0.00964955 A CCNA1 cyclin Al 2.633936 0.01471915 L CH 1 leucine-rich repeats and calponin homology (CH) 2.632229 0.0003 883 domain containing 1 DUSP8 dual specificity phosphatase 8 2.6292 0.01 137426 TIA T-cell lymphoma invasion and metastasis 1 2.626128 0.03662284 CLPTM1 CLPTMl-like 2.601228 0.03868694 L S L SCL/TAL1 interrupting locus 2.59729 0.0397914 TNP03 transportin 3 2.593873 0.00926626 SYMPK symplekin 2.587307 0.03074672 CCNT2 cyclin T2 2.569067 0.04655543 NR neuropilin 1 2.560962 0.02981305 SHQ1 SHQ1 homolog (S. cerevisiae) 2.555645 0.02299193 MAP7D1 MAP7 domain containing 1 2.54933 0.01099938 TECPR2 tectonin beta-propeller repeat containing 2 2.542771 0.04968312 MED23 mediator complex subunit 23 2.540537 0.04879873 ATXN10 ataxin 10 2.539384 0.03524992 DGKA diacylglycerol kinase, alpha 80kDa 2.529001 0.0313754 KIAA024 KIAA0247 2.523791 0.00087761 7 SNAP29 synaptosomal-associated protein, 29kDa 2.51839 0.04622785 RAB31 RAB3 1, member RAS oncogene family 2.516195 0.01067045 SSH3 slingshot homolog 3 (Drosophila) 2.50875 0.04233709 C12orf41 chromosome 12 open reading frame 4 1 2.503165 0.03954708 TTLL1 #N/A 2.496067 0.01179622 HIP 2 Homeodomain interacting protein kinase 2 2.494198 0.01556645 DDOST dolichyl-diphosphooligosaccharide—protein 2.491522 0.04739844 glycosyltransferase PRPF38A PRP38 pre-mRNA processing factor 38 (yeast) 2.486744 0.03023817 domain containing A PFKM phosphofructokinase, muscle 2.486039 0.01023407 SEC23B Sec23 homolog B (S. cerevisiae) 2.485522 0.01805283 ABHD1 1 abhydrolase domain containing 11 2.485291 0.0361806 CCNL2 cyclin L2 2.48232 0.03744227 MTRR 5-methyltetrahydrofolate-homocysteine 2.481257 0.02012838 methyltransferase reductase NRCAM neuronal cell adhesion molecule 2.480739 0.04752255 UBR4 ubiquitin protein ligase E3 component n-recognin 2.479947 0.01080766 4 CDC42BP CDC42 binding protein kinase beta (DMPK-like) 2.475429 0.03133293 B DPP3 dipeptidyl-peptidase 3 2.475017 0.03076931 FN1 fibronectin 1 2.470361 0.04517357 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest Symbol Change value MTERFD MTERF domain containing 2 2.468774 0.0476033 2 MRPL20 Mitochondrial ribosomal protein L20 2.457955 0.03422195 TD D5 tudor domain containing 5 2.453438 0.02693238 TUBA3E #N/A 2.448859 0.03693353 WWP2 WW domain containing E3 ubiquitin protein 2.447361 0.01863292 ligase 2 CDC 16 #N/A 2.444693 0.04661557 SLC28A2 #N/A 2.443784 0.00364928 Magmas Mitochondria-associated protein involved in 2.443612 0.01427752 granulocyte-macrophage colony-stimulating factor signal transduction CDKL5 cyclin-dependent kinase-like 5 2.442396 0.03637012 PCSK7 proprotein convertase subtilisin/kexin type 7 2.441475 0.00070709 KCTD7 potassium channel tetramerisation domain 2.439878 0.0215569 containing 7 FAM129B family with sequence similarity 129, member B 2.436956 0.02104844 IFITM3 #N/A 2.435717 0.04163527 BAI2 brain-specific angiogenesis inhibitor 2 2.42976 0.00770509 MCRS1 microspherule protein 1 2.42666 0.04946973 LAD1 ladinin 1 2.425137 0.03088459 EDF1 #N/A 2.424154 0.04204104 KLHL 12 kelch-like 1 (Drosophila) 2.41491 0.01191345 NUBPL nucleotide binding protein-like 2.410654 0.01757646 LCN10 #N/A 2.410291 0.00584889 ULBP2 #N/A 2.405626 0.02840472 HMCN1 hemicentin 1 2.404099 0.00163052 CD44 CD44 molecule (Indian blood group) 2.403065 0.0344324 INVS inversin 2.402863 0.01659962 ITGB6 integrin, beta 6 2.391807 0.02136789 RFX3 #N/A 2.390793 0.01644792 MCF2L #N/A 2.388832 0.00513299 NICNl nicolin 1 2.388529 0.00908688 PCGF1 polycomb group ring finger 1 2.386976 0.03418426 TNPOl transportin 1 2.3849 0.03820035 TECPR1 tectonin beta-propeller repeat containing 1 2.383271 0.04004739 FEZ1 #N/A 2.382444 0.01408375 YY1AP1 YY1 associated protein 1 2.382036 0.0456202 CPE carboxypeptidase E 2.379491 0.02678441 EHMT1 euchromatic histone-lysine N-methyltransferase 1 2.378332 0.00038361 NDUFAF NADH dehydrogenase (ubiquinone) 1 alpha 2.378237 0.00163131 1 subcomplex, assembly factor 1 MLH3 mutL homolog 3 (E. coli) 2.376897 0.00584984 CKAP2L cytoskeleton associated protein 2-like 2.375931 0.04127031 PYROXD pyridine nucleotide-disulphide oxidoreductase 2.370243 0.04256643 2 domain 2 WDFY2 WD repeat and FYVE domain containing 2 2.369515 0.01867335 NANOS1 nanos homolog 1 (Drosophila) 2.369388 0.02870312 SUMF2 sulfatase modifying factor 2 2.365256 0.04452999 MYST2 MYST histone acetyltransferase 2 2.363382 0.0251515 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ZNF287 zinc finger protein 287 2.355907 0.04074512 CDS2 CDP-diacylglycerol synthase (phosphatidate 2.352796 0.04019579 cytidylyltransferase) 2 EPHX1 epoxide hydrolase 1, microsomal (xenobiotic) 2.352754 0.01354618 SNAPIN SNAP-associated protein 2.35105 0.04268937 THAP1 1 THAP domain containing 1 2.350904 0.02869954 HSD17B7 Hydroxysteroid (17-beta) dehydrogenase 7 2.346188 0.02274892 P2 pseudogene 2 TNIP2 TNFAIP3 interacting protein 2 2.342348 0.03096003 SFX 1 sideroflexin 1 2.34231 0.04322009 RNFT2 ring finger protein, transmembrane 2 2.341714 0.02755541 SOLH small optic lobes homolog (Drosophila) 2.33619 0.04058995 LRBA LPS-responsive vesicle trafficking, beach and 2.334046 0.03741658 anchor containing ANK D 1 ankyrin repeat domain 1 2.332943 0.01490882 1 SPDYE8P speedy homolog E8 (Xenopus laevis), pseudogene 2.327864 0.04429203 PHC3 polyhomeotic homolog 3 (Drosophila) 2.327043 0.04774561 PPP5C protein phosphatase 5, catalytic subunit 2.32173 0.04246803 DFNB31 Deafness, autosomal recessive 31 2.321 165 0.00480601 SLC25A3 solute carrier family 25, member 35 2.319554 0.01088912 5 HISPPD2 Histidine acid phosphatase domain containing 2A 2.316541 0.03473277 A SLC25A4 #N/A 2.315244 0.0324995 3 LYG2 lysozyme G-like 2 2.313446 0.03256065 SUSD2 sushi domain containing 2 2.308653 0.00076784 TTC4 tetratricopeptide repeat domain 4 2.305393 0.01134933 PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, 2.30314 0.00122676 alpha MZF1 myeloid zinc finger 1 2.300058 0.0424067 TNNT3 troponin T type 3 (skeletal, fast) 2.299284 0.00978502 ELOVL6 ELOVL family member 6, elongation of long 2.298864 0.02905437 chain fatty acids (FENl/Elo2, SUR4/Elo3-like, yeast) KIAA009 KIAA0090 2.294906 0.00981731 0 BFAR bifunctional apoptosis regulator 2.293413 0.00416696 IFT122 intraflagellar transport 122 homolog 2.286489 0.04948514 (Chlamydomonas) CDCA7L cell division cycle associated 7-like 2.28315 0.00620642 A APC1 anaphase promoting complex subunit 1 2.282745 0.0410648 C5orf25 chromosome 5 open reading frame 25 2.282417 0.04256676 AP3M2 #N/A 2.281407 0.02326857 R F 115 ring finger protein 115 2.28131 0.04092934 OSBPL1A oxysterol binding protein-like 1A 2.28078 0.03304009 SMARCB SWI/SNF related, matrix associated, actin 2.279405 0.0346208 1 dependent regulator of chromatin, subfamily b, member 1 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value FAM53C family with sequence similarity 53, member C 2.279002 0.02147619 SLC4A7 solute carrier family 4, sodium bicarbonate 2.276701 0.00738148 cotransporter, member 7 CYB5R3 cytochrome b5 reductase 3 2.273478 0.00146646 ΗΓΝΤ2 histidine triad nucleotide binding protein 2 2.272342 0.02016666 CTNNB 1 catenin (cadherin-associated protein), beta , 2.268497 0.00091218 88kDa LR IB low density lipoprotein receptor-related protein 1B 2.268244 0.01037608 SYTL2 Synaptotagmin-like 2 2.266834 0.04720219 Clorf55 chromosome 1 open reading frame 55 2.266459 0.02062753 DOT1L DOTl-like, histone H3 methyltransferase (S. 2.266164 0.04398079 cerevisiae) PRUNE prune homolog (Drosophila) 2.261951 0.04105039 TCP1 1L2 t-complex (mouse)-like 2 2.260427 0.03597573 ABCG2 ATP-binding cassette, sub-family G (WHITE), 2.258303 0.02678408 member 2 NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha 2.255936 0.0162317 3 subcomplex, 13 EIF2B5 eukaryotic translation initiation factor 2B, subunit 2.254942 0.04669815 5 epsilon, 82kDa TCP1 1L1 #N/A 2.252361 0.02498018 TULP3 tubby like protein 3 2.252197 0.03918548 PLCG2 phospholipase C, gamma 2 (phosphatidylinositol- 2.251615 0.03035352 specific) CLEC2D C-type lectin domain family 2, member D 2.250092 0.03239425 MAPKAP #N/A 2.247765 0.01969152 K5 DCTN1 dynactin 1 (pi 50, glued homolog, Drosophila) 2.247297 0.0361356 NF1 neurofibromin 1 2.246597 0.04162672 SIPA1L2 signal-induced proliferation-associated 1 like 2 2.244631 0.03842635 C9orf97 Chromosome 9 open reading frame 97 2.244268 0.00859059 CTSH #N/A 2.244056 0.03205423 CDKN 1A cyclin-dependent kinase inhibitor 1A (p21, Cip 1) 2.238879 0.01566499 SYNJ2 synaptojanin 2 2.238072 0.02730281 NCOA1 nuclear receptor coactivator 1 2.235876 0.0373691 SLC37A3 solute carrier family 37 (glycerol-3-phosphate 2.235513 0.04866478 transporter), member 3 MGAT4B mannosyl (alpha-l,3-)-glycoprotein beta-l,4-N- 2.233658 0.04886326 acetylglucosaminyltransferase, isozyme B ABLIM3 actin binding LIM protein family, member 3 2.231371 0.0235566 MAP 1B microtubule-associated protein 1B 2.227853 0.00050307 GPR87 G protein-coupled receptor 87 2.225246 0.04203909 SGSM2 small G protein signaling modulator 2 2.223093 0.01792753 HSDL2 hydroxysteroid dehydrogenase like 2 2.220989 0.04626046 WARS2 tryptophanyl tRNA synthetase 2, mitochondrial 2.216981 0.00420204 PIGA #N/A 2.215978 0.02372293 HAGHL Hydroxyacylglutathione hydrolase-like 2.210443 0.04351155 ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat 2.210235 0.03732842 and PH domain 2 OPA3 Optic atrophy 3 (autosomal recessive, with chorea 2.209787 0.00171029 DBl/ 694375 16 . 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value and spastic paraplegia) CHRM3 #N/A 2.209625 0.02107095 C3orf23 chromosome 3 open reading frame 23 2.209375 0.01667732 PHF8 PHD finger protein 8 2.206374 0.0307203 TMEM18 transmembrane protein 189 2.206157 0.02937023 9 ZFYVE27 #N/A 2.205437 0.0258554 DENND2 DENN/MADD domain containing 2C 2.203543 0.04263647 C STRADA STE20-related kinase adaptor alpha 2.203056 0.02903358 TCTN1 tectonic family member 1 2.200135 0.02398527 MUT methylmalonyl CoA mutase 2.19871 1 0.04875338 RICS Rho GTPase-activating protein 2.198536 0.03531902 SEC14L2 SEC14-like 2 (S. cerevisiae) 2.197791 0.02157167 GIMAP6 GTPase, IMAP family member 6 2.197772 0.019591 13 BCORL1 BCL6 co-repressor-like 1 2.1931 11 0.02543076 C19orf62 chromosome 1 open reading frame 62 2.191676 0.03154505 FIG4 FIG4 homolog, SAC1 lipid phosphatase domain 2.191472 0.01514057 containing (S. cerevisiae) FBXL13 F-box and leucine-rich repeat protein 13 2.18993 0.02806166 ECE1 endothelin converting enzyme 1 2.189231 0.01296876 NT5DC2 5'-nucleotidase domain containing 2 2.188765 0.028676 CNOT6L CCR4-NOT transcription complex, subunit 6-like 2.188121 0.00901903 TCEA2 transcription elongation factor A (SII), 2 2.187952 0.04357233 ERLIN2 ER lipid raft associated 2 2.184886 0.01319339 ITIH5L inter-alpha (globulin) inhibitor H5-like 2.183908 0.04573874 ZNF384 zinc finger protein 384 2.181926 0.0096138 ADCY1 adenylate cyclase 1 (brain) 2.180825 0.043061 17 MSI1 #N/A 2.180303 0.01207864 WDR22 WD repeat domain 22 2.180082 0.02028217 FBXL3 F-box and leucine-rich repeat protein 3 2.17691 1 0.01974647 NPR1 natriuretic peptide receptor A/guanylate cyclase A 2.176805 0.02348208 (atrionatriuretic peptide receptor A) NBAS neuroblastoma amplified sequence 2.176022 0.03688986 ERCC3 excision repair cross-complementing rodent repair 2.175934 0.00899813 deficiency, complementation group 3 (xeroderma pigmentosum group B complementing) C6orfl06 chromosome 6 open reading frame 106 2.174662 0.01419501 CACNA1 calcium channel, voltage-dependent, L type, alpha 2.170782 0.00748575 D ID subunit C7orf41 chromosome 7 open reading frame 1 2.170586 0.04491985 DENND4 DENN/MADD domain containing 4C 2.170566 0.01230614 C MYCBP2 MYC binding protein 2 2.168534 0.02526474 KIAA056 KIAA0562 2.167178 0.01401037 2 EFTUD1 elongation factor Tu GTP binding domain 2.166378 0.01642407 containing 1 SP140 SP140 nuclear body protein 2.164286 0.04002558 MRPL19 mitochondrial ribosomal protein LI9 2.163857 0.02878438 DB1/ 69 37516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value IRF7 interferon regulatory factor 7 2.163552 0.01010416 SCFD2 seel family domain containing 2 2.163273 0.04389159 GDAP1L1 Ganglioside-induced differentiation-associated 2.162375 0.03060397 protein 1-like 1 TMEM67 transmembrane protein 67 2.161969 0.02357079 PSME3 proteasome (prosome, macropain) activator 2.161553 0.03295222 subunit 3 (PA28 gamma; Ki) KIF1B kinesin family member 1B 2.160942 0.02563078 RUVBL1 RuvB-like 1 (E. coli) 2.159586 0.03309362 PTGR1 prostaglandin reductase 1 2.158659 0.00752827 COG5 component of oligomeric golgi complex 5 2.157755 0.0404852 RPAP1 RNA polymerase II associated protein 1 2.156564 0.01591496 TMEM18 transmembrane protein 184A 2.155301 0.02641933 4A Clorfl57 #N/A 2.15439 0.03582529 PSMA2 proteasome (prosome, macropain) subunit, alpha 2.153033 0.01873174 type, 2 FNBP1 formin binding protein 1 2.152364 0.02691663 PAK3 p21 protein (Cdc42/Rac)-activated kinase 3 2.151948 0.01846905 CHST10 carbohydrate sulfotransferase 10 2.151551 0.02781973 HIST1H2 /A 2.151 105 0.03021859 AI TP53BP2 tumor protein p53 binding protein, 2 2.150413 0.0349378 PEX1 1A peroxisomal biogenesis factor 1 alpha 2.150314 0.03310421 CLTCL1 clathrin, heavy chain-like 1 2.149373 0.03834021 MAP3 5 mitogen-activated protein kinase kinase kinase 5 2.14786 0.00358042 TBC1D5 TBC1 domain family, member 5 2.146839 0.00272191 LRRC16A leucine rich repeat containing 16A 2.14675 0.02601013 ZNF318 zinc finger protein 318 2.146698 0.04063381 CNTFR ciliary neurotrophic factor receptor 2.146664 0.03768583 ARHGEF Rho guanine nucleotide exchange factor (GEF) 12 2.145732 0.00866423 12 CALCA #N/A 2.145508 0.03035912 DOCK7 dedicator of cytokinesis 7 2.144975 0.01593592 CCT3 chaperonin containing TCP1, subunit 3 (gamma) 2.143663 0.03791006 FANCI Fanconi anemia, complementation group I 2.143024 0.03029496 ST3GAL5 ST3 beta-galactoside alpha-2,3-sialyltransferase 5 2.141182 0.00246875 BCL2L14 BCL2-like 1 (apoptosis facilitator) 2.140794 0.04084361 PRKCI protein kinase C, iota 2.14033 0.01913295 LIG3 ligase III, DNA, ATP-dependent 2.139885 0.00637983 KRT16 keratin 16 2.136947 0.0357481 STARD5 StAR-related lipid transfer (START) domain 2.135108 0.01409282 containing 5 TPD52 tumor protein D52 2.134887 0.03438915 TNS1 tensin 1 2.133585 0.02192764 NACAP1 nascent-polypeptide-associated complex alpha 2.13347 0.04814159 polypeptide pseudogene 1 ANTXR1 anthrax toxin receptor 1 2.131767 0.03135031 KCNK18 #N/A 2.131568 0.03880469 NIACRl #N/A 2.130256 0.01031739 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CHD1L chromodomain helicase DNA binding protein 1- 2.12969 0.00196612 like PHLDB2 pleckstrin homology-like domain, family B, 2.129192 0.0359393 member 2 TGFBI transforming growth factor, beta-induced, 68kDa 2.12691 0.03594676 DDX42 DEAD (Asp-Glu- Ala-Asp) box polypeptide 42 2.125766 0.03480201 TULP4 tubby like protein 4 2.1251 1 0.00579006 EXOC4 exocyst complex component 4 2.124352 0.03322826 TAF 1A TATA box binding protein (TBP)-associated 2.123803 0.01221043 factor, RNA polymerase I, A, 48kDa C3orf34 chromosome 3 open reading frame 34 2.123355 0.0105264 DOCK6 dedicator of cytokinesis 6 2.123338 0.00285469 ETFDH electron-transferring-flavoprotein dehydrogenase 2.122325 0.02860394 KDM5A lysine (K)-specific demethylase 5A 2.121029 0.01623086 T IT tR A isopentenyltransferase 1 2.120578 0.02390976 KIR2DS4 #N/A 2.1 1998 0.01305444 LATS2 LATS, large tumor suppressor, homolog 2 2.119657 0.02938295 (Drosophila) ANKRD2 ankyrin repeat domain 27 (VPS9 domain) 2.11918 0.02611 183 7 ANKS A ankyrin repeat and sterile alpha motif domain 2. 19086 0.04136303 containing 1A ASXL2 additional sex combs like 2 (Drosophila) 2.1 16091 0.04307021 MAN2A1 mannosidase, alpha, class 2A, member 1 2.1 15693 0.03192584 PE 1 peroxisomal biogenesis factor 1 2.1 14996 0.00307576 TUB tubby homolog (mouse) 2.1 14292 0.00094413 MAP3K4 mitogen-activated protein kinase kinase kinase 4 2.1 14067 0.02121523 ZNF23 5 zinc finger protein 235 2.1 13243 0.04503107 HARBI1 #N/A 2.113096 0.03103975 POLR3C polymerase (RNA) III (DNA directed) polypeptide 2.1 1243 0.04340473 C (62kD) FLOT2 #N/A 2.1 11448 0.04280161 PARN poly(A)-specific ribonuclease (deadenylation 2.1 11073 0.03680447 nuclease) TRIP 12 thyroid hormone receptor interactor 12 2.109385 0.0351422 LSG1 large subunit GTPase 1 homolog (S. cerevisiae) 2.107797 0.03808136 LHPP #N/A 2.10708 0.04218035 H2AFY H2A histone family, member Y 2.106526 0.03868839 GLB1 galactosidase, beta 1 2.105544 0.0320468 CNOT4 CCR4-NOT transcription complex, subunit 4 2.103723 0.0261 1243 SPG20 spastic paraplegia 20 (Troyer syndrome) 2.103392 0.00306415 DAP3 death associated protein 3 2.103304 0.03983598 UBR1 Ubiquitin protein ligase E3 component n-recognin 2.103247 0.04650921 1 MPDU1 mannose-P-dolichol utilization defect 1 2.102917 0.01760447 P4HA2 prolyl 4-hydroxylase, alpha polypeptide II 2.102565 0.03821474 PHF23 #N/A 2.10236 0.00738597 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), 2.100129 0.028971 member 4 GM2A GM2 ganglioside activator 2.099143 0.03785905 DB1/ 69437 5 16.1 Supplemental Table 2 Gene Transcripts Upreguiated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ZFYVE26 zinc finger, FYVE domain containing 26 PARP1 poly (ADP-ribose) polymerase 1 DPYSL5 dihydropyrimidinase-like 5 EXOC6 exocyst complex component 6 FAM48A family with sequence similarity 48, member A RPA2 replication protein A2, 32kDa ANKH ankylosis, progressive homolog (mouse) MRPS22 Mitochondrial ribosomal protein S22 SLC5A8 #N/A SPR sepiapterin reductase (7,8- dihydrobiopterin:NADP+ oxidoreductase) FBXW1 1 F-box and WD repeat domain containing 11 PCSK4 Proprotein convertase subtilisin/kexin type 4 SPON1 spondin 1, extracellular matrix protein HJURP Holliday junction recognition protein DNAJB6 DnaJ (Hsp40) homolog, subfamily B, member 6 BDH2 3-hydroxybutyrate dehydrogenase, type 2 LTB4R2 leukotriene B4 receptor 2 ZNF638 zinc finger protein 638 THAP1 THAP domain containing, apoptosis associated protein 1 PRKCD protein kinase C, delta TMC2 transmembrane channel-like 2 PITPNM1 phosphatidylinositol transfer protein, membrane- associated 1 FAM1 14A family with sequence similarity 114, member Al 1 FIS1 fission 1 (mitochondrial outer membrane) homolog (S. cerevisiae) DYM dymeclin PPARA peroxisome proliferator-activated receptor alpha HOXB2 #N/A GGA3 #N/A FAR 1 FERM, RhoGEF (ARHGEF) and pleckstrin domain protein 1 (chondrocyte-derived) GNPDA1 glucosamine-6-phosphate deaminase 1 C16orf35 chromosome 16 open reading frame 35 SLC25A3 #N/A 3 ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 MYH11 myosin, heavy chain 11, smooth muscle DCLRE1 DNA cross-link repair 1A (PS02 homolog, S. A cerevisiae) C4orf41 chromosome 4 open reading frame 1 MYH9 myosin, heavy chain 9, non-muscle SNCAIP synuclein, alpha interacting protein FAM1 17A family with sequence similarity 117, member A PRDX3 peroxiredoxin 3 RP9 retinitis pigmentosa 9 (autosomal dominant) DBl/ 69437516. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value LRP10 low density lipoprotein receptor-related protein 10 2.065981 0.04553922 ERAL1 N/A 2.065922 0.04248234 GPR125 G protein-coupled receptor 1 5 2.064453 0.01530749 ZP3 zona pellucida glycoprotein 3 (sperm receptor) 2.064019 0.00642625 TRAF3IP TNF receptor-associated factor 3 interacting 2.063173 0.03736506 1 protein 1 GTPBP1 GTP binding protein 1 2.063154 0.02305996 MACF1 microtubule-actin crosslinking factor 1 2.062381 0.03102047 CLGN calmegin 2.062335 0.00884516 SH2B1 SH2B adaptor protein 1 2.061791 0.00890218 JAG1 Jagged 1 (Alagille syndrome) 2.061732 0.04527461 CAST calpastatin 2.061296 0.04598394 ERG v-ets erythroblastosis virus E26 oncogene 2.060672 0.00751355 homolog (avian) SCPEP1 serine carboxypeptidase 1 2.060543 0.03705332 COPA coatomer protein complex, subunit alpha 2.060237 0.01659317 WDR17 WD repeat domain 17 2.059102 0.03201935 NKAIN1 #N/A 2.057883 0.03463659 DDX19B DEAD (Asp-Glu-Ala-As) box polypeptide 19B 2.057343 0.02376143 SMARCA SWI/SNF related, matrix associated, actin 2.057319 0.02557869 L dependent regulator of chromatin, subfamily a-like 1 PCGF3 polycomb group ring finger 3 2.057016 0.01483219 CAPN2 calpain 2, (m/II) large subunit 2.056544 0.0491258 FLJ40504 keratin 18 pseudogene 2.05585 0.04756887 BRI3 brain protein 13 2.055766 0.04249244 PPP2R5C protein phosphatase 2, regulatory subunit B', 2.055208 0.02721621 gamma GANAB Glucosidase, alpha; neutral AB 2.054564 0.04775384 TSPAN1 tetraspanin 1 2.052889 0.02243325 HACL1 2-hydroxyacyl-CoA lyase 1 2.052224 0.04582893 CCDC126 coiled-coil domain containing 126 2.05198 0.00386287 MCM9 minichromosome maintenance complex 2.051018 0.01929319 component 9 POLR2A polymerase (RNA) II (DNA directed) polypeptide 2.049273 0.01201635 A, 220kDa MATK megakaryocyte-associated tyrosine kinase 2.048784 0.04855365 TBC1D10 #N/A 2.046411 0.04126805 A FOXJ3 forkhead box J3 2.045612 0.02462986 KIAA184 KIAA1841 2.04433 0.02550558 1 TBC1D19 TBC1 domain family, member 19 2.043551 0.00198919 BOD1 biorientation of chromosomes in cell division 1 2.043392 0.03367415 SENP8 #N/A 2.043162 0.01143988 SLC16A4 solute carrier family 16, member 4 2.043144 0.03742794 (monocarboxylic acid transporter 5) TMEM50 transmembrane protein 50B 2.0431 0.03853038 B C9orf96 chromosome 9 open reading frame 96 2.039984 0.01602301 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ENTPD1 #N/A 2.039157 0.0157279 TGFBRA transforming growth factor, beta receptor 2.039078 0.02002439 PI associated protein 1 FRMD6 FERM domain containing 6 2.038562 0.03525536 POLR3A polymerase (RNA) III (DNA directed) polypeptide 2.037793 0.047341 6 1 A, 155kDa NUP133 nucleoporin 133kDa 2.036795 0.031 18442 ICOSLG #N/A 2.036312 0.01273721 DDIT3 DNA-damage-inducible transcript 3 2.035672 0.01260509 DULLAR dullard homolog (Xenopus laevis) 2.034606 0.02967567 D KIAA132 KIAA1324-like 2.034493 0.00645901 4L TEL02 TEL2, telomere maintenance 2, homolog (S. 2.033902 0.01009688 cerevisiae) AGFG2 ArfGAP with FG repeats 2 2.031856 0.03916018 CFH complement factor H 2.030595 0.03036614 C9orf5 chromosome 9 open reading frame 5 2.030239 0.03586119 TMEM18 transmembrane protein 183A 2.029282 0.017361 17 3A CRTAC1 #N/A 2.027223 0.01696305 HIST1H2 histone cluster 1, H2be 2.024897 0.0278084 BE DDX10 DEAD (Asp-Glu-Ala-Asp) box polypeptide 0 2.02467 0.03369673 DCBLD2 discoidin, CUB and LCCL domain containing 2 2.023168 0.02449477 WDR54 WD repeat domain 54 2.023059 0.0430325 IGSF1 immunoglobulin superfamily, member 1 2.022907 0.0217968 FAM65A family with sequence similarity 65, member A 2.022344 0.00515737 NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha 2.021916 0.02265365 0 subcomplex, 10, 42kDa CTPS CTP synthase 2.020961 0.0454319 PAPD4 PAP associated domain containing 4 2.019495 0.04008597 GALNT2 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 2.019375 0.0343144 N-acetylgalactosaminyltransferase 2 (GalNAc-T2) CUL7 cullin 7 2.019007 0.02526261 PLEKHG pleckstrin homology domain containing, family G 2.018739 0.0133122 2 (with RhoGef domain) member 2 SERI C5 serine incorporator 5 2.018135 0.0401226 TTC37 tetratricopeptide repeat domain 37 2.015973 0.01897095 LIMK2 LIM domain kinase 2 2.015851 0.01966932 BTBD12 #N/A 2.015237 0.03720552 FAM5B family with sequence similarity 5, member B 2.014759 0.01820992 DOCK8 dedicator of cytokinesis 8 2.014412 0.00434593 RILPL1 #N/A 2.013918 0.02071449 GLUL glutamate-ammonia ligase 2.013353 0.01359148 ALDH9A aldehyde dehydrogenase 9 family, member A l 2.013125 0.03374331 1 SQRDL sulfide quinone reductase-like (yeast) 2.012745 0.00681842 PIGN phosphatidylinositol glycan anchor biosynthesis, 2.012066 0.03637931 class N D 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value EFHC1 EF-hand domain (C-terminal) containing 1 2.01 173 0.01468961 VPS13D vacuolar protein sorting 13 homolog D (S. 2.01 1571 0.01703863 cerevisiae) AHI1 Abelson helper integration site 1 2.01 1165 0.04965523 ZFYVE9 zinc finger, FYVE domain containing 9 2.010537 0.03963952 MED 15 mediator complex subunit 15 2.009871 0.0046975 TARS2 threonyl-tRNA synthetase 2, mitochondrial 2.009722 0.04831308 (putative) RNASE4 #N/A 2.009656 0.00740801 HDAC6 histone deacetylase 6 2.009034 0.02420665 ATG9B ATG9 autophagy related 9 homolog B (S. 2.008936 0.04422972 cerevisiae) CXCL5 #N/A 2.00891 0.03149128 I PP5J inositol polyphosphate-5 -phosphatase J 2.008428 0.00203254 PEX19 peroxisomal biogenesis factor 19 2.008181 0.00973182 TRIM24 tripartite motif-containing 24 2.007807 0.03950043 TRAF3IP TRAF3 interacting protein 2 2.007532 0.0181211 1 2 10-Sep #N/A 2.005107 0.04938754 ELF2 E74-like factor 2 (ets domain transcription factor) 2.004646 0.01763801 FLJ20674 Hypothetical protein FLJ20674 2.004557 0.00432274 OSMR oncostatin M receptor 2.002788 0.04071 16 CLEC18A C-type lectin domain family 18, member A 2.002304 0.04924147 BET1L #N/A 2.00183 0.04957609 PAOX polyamine oxidase (exo-N4-amino) 1.99911 0.00673077 PRICKLE prickle homolog 3 (Drosophila) 1.999055 0.01952605 3 HPCAL1 hippocalcin-like 1 1.998674 0.0076982 TSPAN31 tetraspanin 3 1 1.998064 0.04403488 KIR3DL2 killer cell immunoglobulin-like receptor, three 1.997355 0.0368632 domains, long cytoplasmic tail, 2 FBRSL1 fibrosin-like 1 1.996861 0.01347891 C17orf81 chromosome 17 open reading frame 81 1.996773 0.04433268 LOC2205 #N/A 1.996635 0.01160697 94 MAP3K12 mitogen-activated protein kinase kinase kinase 12 1.995475 0.0264 1934 ATP9B ATPase, class II, type 9B 1.995294 0.04583778 F8A1 #N/A 1.99508 0.04250009 ACSL1 acyl-CoA synthetase long-chain family member 1 1.995074 0.0008948 1 CELA3B #N/A 1.99442 0.01533788 SLC30A7 solute carrier family 30 (zinc transporter), member 1.993271 0.03666306 7 PRMT3 protein arginine methyltransferase 3 1.992162 0.00863879 PAM peptidylglycine alpha-amidating monooxygenase 1.991505 0.00094873 PDHX pyruvate dehydrogenase complex, component X 1.991377 0.04243255 ADCY3 adenylate cyclase 3 1.991273 0.00529787 FAM114A family with sequence similarity 114, member A2 1.990681 0.01035328 2 NKX3-1 NK3 homeobox 1 1.990583 0.01359758 MPPED2 metallophosphoesterase domain containing 2 1.989438 0.04218865 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Uprcgulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value WDR19 WD repeat domain 1.988941 0.03821 171 FRAS1 Fraser syndrome 1 1.9881 11 0.03074444 MCCC2 Methylcrotonoyl-Coenzyme A carboxylase 2 1.986557 0.01821922 (beta) ANO10 anoctamin l O 1.985731 0.00025163 SEMA3A sema domain, immunoglobulin domain (Ig), short 1.984479 0.00549881 basic domain, secreted, (semaphorin) 3A SIL1 SIL1 homolog, endoplasmic reticulum chaperone 1.984176 0.0093771 (S. cerevisiae) LONRF1 LON peptidase N-terminal domain and ring finger 1.983508 0.00345862 1 WDR85 #N/A 1.983297 0.03091787 ITFG3 integrin alpha FG-GAP repeat containing 3 1.983129 0.04260644 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene 1.981818 0.04875523 homolog 3 (avian) PREB prolactin regulatory element binding 1.981672 0.02852565 ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1.981336 0.01844171 1 CSPP1 centrosome and spindle pole associated protein 1 1.981269 0.04082699 SDHB succinate dehydrogenase complex, subunit B, iron 1.980256 0.00952515 sulfur (Ip) MIF #N/A 1.979778 0.01765393 ELAC2 elaC homolog 2 (E. coli) 1.979383 0.00409566 APC adenomatous polyposis coli 1.978957 0.02642031 LOC2601 Viral DNA polymerase-transactivated protein 6 1.978739 0.04497948 0 SLC39A1 solute carrier family 39 (zinc transporter), member 1.978355 0.02888006 2 12 STX12 syntaxin l 2 1.977998 0.03106077 TMEM19 transmembrane protein 198 1.977707 0.0168314

SHROOM shroom family member 3 1.977414 0.01628976 3 SGCG sarcoglycan, gamma (35kDa dystrophin-associated 1.976029 0.04872242 glycoprotein) CD109 CD 109 molecule 1.975962 0.03780495 TRPV5 transient receptor potential cation channel, 1.975926 0.01142992 subfamily V, member 5 NFX1 nuclear transcription factor, X-box binding 1 1.974681 0.03204951 RASAL2 RAS protein activator like 2 1.974273 0.00945316 MYOIC myosin IC 1.973502 0.03292925 FAT1 FAT tumor suppressor homolog 1 (Drosophila) 1.973257 0.03471174 APP amyloid beta (A4) precursor protein 1.973232 0.03396235 TRPM6 transient receptor potential cation channel, 1.972804 0.02966632 subfamily M, member 6 CEP 192 centrosomal protein 192kDa 1.972566 0.04466506 ARHGAP Rho GTPase activating protein 18 1.971624 0.03244688 18 C14orfl #N/A 1.97125 0.03550573 ADAR adenosine deaminase, RNA-specific 1.970478 0.02323278 DBl/ 694375 16. Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PFKFB2 6-phosphofructo-2-kinase/fructose-2,6- 1.970015 0.00399819 biphosphatase 2 RLF rearranged L-myc fusion 1.969754 0.01353227 SSFA2 sperm specific antigen 2 1.968486 0.01548873 hCG_1640 #N/A 1.966671 0.03863105 171 FOS #N/A 1.965857 0.03362548 CLMN calmin (calponin-like, transmembrane) 1.965204 0.00532298 EIF4E2 eukaryotic translation initiation factor 4E family 1.965165 0.0200992 member 2 MAML1 mastermind-like 1 (Drosophila) 1.965045 0.02968616 HIST2H4 histone cluster 2, H4a 1.964463 0.04156608 A TMEM20 transmembrane protein 208 1.963724 0.01715938 8 MED 12 mediator complex subunit 12 1.963442 0.04534554 OPTN Optineurin 1.963237 0.02282148 EXOC7 exocyst complex component 7 1.962978 0.00819659 ZNF530 #N/A 1.962974 0.02809778 DST dystonin 1.962826 0.0356846 DOPEY 1 dopey family member 1 1.962635 0.00936706 ZNF669 zinc finger protein 669 1.962251 0.01307985 ZNF664 zinc finger protein 664 1.961938 0.02541237 TTC21B tetratricopeptide repeat domain 2IB 1.960637 0.00300804 PPM1K protein phosphatase, Mg2+/Mn2+ dependent, IK 1.960567 0.03170998 PDE8A phosphodiesterase 8A 1.960537 0.01873747 SPDEF SAM pointed domain containing ets transcription 1.960452 0.0390656 factor C13orf34 chromosome 13 open reading frame 34 1.960428 0.03422755 PMEPA1 prostate transmembrane protein, androgen induced 1.959469 0.03570985 1 MEDIO mediator complex subunit 10 1.9594 0.03380336 AMELX amelogenin, X-linked 1.959231 0.04580962 AGA aspartylglucosaminidase 1.958962 0.02627481 COL6A2 collagen, type VI, alpha 2 1.95896 0.03531084 UXS1 UDP-glucuronate decarboxylase 1 1.958751 0.03336713 UGCG UDP-glucose ceramide glucosyltransferase 1.958597 0.01999611 WD 93 WD repeat domain 93 1.958538 0.01358497 CPLX2 complexin 2 1.957912 0.04856893 CHFR Checkpoint with forkhead and ring finger domains 1.957518 0.01016181 SAMD 10 sterile alpha motif domain containing 10 1.956836 0.03784731 KCNH1 potassium voltage-gated channel, subfamily H 1.95678 0.01184592 (eag-related), member 1 KIAA124 KIAA1244 1.956128 0.02848508 4 SMAD7 SMAD family member 7 1.955983 0.016347 NCAPG2 non-SMC condensin II complex, subunit G2 1.955733 0.00123487 KIF13B kinesin family member 13B 1.954903 0.00695187 ZFP36L2 #N/A 1.954851 0.0013625 SIDT1 SID1 transmembrane family, member 1 1.954674 0.04160414 1/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ATXN1 ataxin l 1.954585 0.02056391 SDF4 #N/A 1.9541 0.01455397 TMEM14 transmembrane protein 144 1.954001 0.02002059 4 EIF3F eukaryotic translation initiation factor 3, subunit F .953937 0.04942974 CCNJ cyclin J 1.953568 0.0307558 BMP6 bone morphogenetic protein 6 1.953407 0.00565919 EXOC2 exocyst complex component 2 1.952472 0.01339535 ASB1 ankyrin repeat and SOCS box-containing 1 .952381 0.03633353 EML2 #N/A 1.952229 0.00541735 PUM1 pumilio homolog 1 (Drosophila) 1.951866 0.0158386 LMLN leishmanolysin-like (metallopeptidase M8 family) 1.951368 0.02521616 TMEM70 transmembrane protein 70 1.950205 0.02384912 SLC25A1 solute carrier family 25, member (citrin) 1.949537 0.043 88595 3 FASN fatty acid synthase 1.948427 0.02462526 PCDHB16 #N/A 1.948418 0.04667535 VTN vitronectin 1.948149 0.00804688 QTRTD1 queuine tRNA-ribosyltransferase domain 1.947974 0.04351918 containing 1 UGT1A1 UDP glucuronosyltransferase 1 family, 1.947405 0.03804037 polypeptide A l GAL Galanin prepropeptide 1.947374 0.03405624 ALG9 asparagine-linked glycosylation 9, alpha- 1,2- 1.947258 0.04996388 mannosyltransferase homolog (S. cerevisiae) FBXL5 F-box and leucine-rich repeat protein 5 1.946953 0.037805 12 DEPDC6 DEP domain containing 6 1.946724 0.02824042 TRAK2 trafficking protein, kinesin binding 2 1.946558 0.00194833 CHD3 chromodomain helicase DNA binding protein 3 1.945989 0.02579796 ANKHD1 ANKHDl-EIF4EBP3 readthrough 1.945791 0.03987177

EIF4EBP3 ZNF512 zinc finger protein 512 1.944769 0.03883459 NPFFR1 neuropeptide FF receptor 1 1.944368 0.00508591 DEN D3 DENN/MADD domain containing 3 1.943696 0.03849635 BST1 bone marrow stromal cell antigen 1 1.943471 0.01376543 BCL2L11 BCL2-like 1 1 (apoptosis facilitator) 1.943373 0.01340632 RASAl RAS p21 protein activator (GTPase activating 1.943062 0.01887466 protein) 1 WNT2B wingless-type MMTV integration site family, 1.942845 0.0305 1607 member 2B DCLRE1 DNA cross-link repair 1C (PS02 homolog, S. 1.942843 0.01560169 C cerevisiae) ETS2 v-ets erythroblastosis virus E26 oncogene 1.942073 0.00217845 homolog 2 (avian) DNASE2 deoxyribonuclease II, lysosomal 1.942024 0.01200752 TRAFD1 TRAF-type zinc finger domain containing 1 1.941 885 0.02871 056 PEX12 #N/A 1.941744 0.04737382 LIMA1 LIM domain and actin binding 1 .94 1669 0.04567907 IMPDH2 IMP (inosine 5'-monophosphate) dehydrogenase 2 1.941513 0.0365507 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value MYPN myopalladin 1.940856 0.00327924 BECN1 beclin 1, autophagy related 1.939624 0.03134078 TRMT12 tR A methyltransferase 2 homolog (S. 1.939237 0.0271696 cerevisiae) WDR47 WD repeat domain 47 1.939015 0.01410477 GLS2 glutaminase 2 (liver, mitochondrial) 1.938232 0.00793526 WDFY4 WDFY family member 4 1.938099 0.03267152 OR8D2 Olfactory receptor, family 8, subfamily D, member 1.938013 0.00598943 9 NCAPD3 non-SMC condensin II complex, subunit D3 1.9371 19 0.04972044 FAT2 FAT tumor suppressor homolog 2 (Drosophila) 1.93697 0.00379669 ROBOl roundabout, axon guidance receptor, homolog 1 1.9367 0.03725501 (Drosophila) FAM131C #N/A 1.936587 0.03934531 PRMT2 protein arginine methyltransferase 2 1.935965 0.01672214 ATP6V0A ATPase, H+ transporting, lysosomal V O subunit a4 1.935551 0.01584305

MY05B myosin VB 1.935376 0.00697742 TTPAL #N/A 1.934954 0.01866925 POLR1A polymerase (RNA) I polypeptide A, 194kDa 1.933999 0.01513979 RPP40 #N/A 1.933671 0.00757301 C20orfl96 chromosome 20 open reading frame 196 1.933501 0.0312781 1 SMYD4 SET and MYND domain containing 4 1.932889 0.0209559 SYNGR4 #N/A 1.932569 0.04184076 MED22 mediator complex subunit 22 1.932531 0.0007351 1 BCKDK #N/A 1.932472 0.03091836 CPEB4 cytoplasmic polyadenylation element binding 1.932187 0.020431 2 protein 4 HOXB3 homeobox B3 1.932022 0.03389903 PDE9A phosphodiesterase 9A 1.930898 0.00997 ILKAP integrin-linked kinase-associated serine/threonine 1.930093 0.04312904 phosphatase 2C FBX032 #N/A 1.928699 0.00876792 OSBPL11 oxysterol binding protein-like 1 1.927606 0.0141209 ZMYM3 #N/A 1.92728 0.0069445 ZZEF1 zinc finger, ZZ-type with EF-hand domain 1 1.927149 0.01667368 ORC1L origin recognition complex, subunit 1-like (yeast) 1.926446 0.04566535 PRR proline rich 14 1.925862 0.03753863 SRBD1 SI RNA binding domain 1 1.925412 0.04260049 GNA12 guanine nucleotide binding protein (G protein) 1.924993 0.00879528 alpha 2 MAPKAP mitogen-activated protein kinase-activated protein 1.924941 0.02799185 2 kinase 2 HMGCR 3-hydroxy-3 -methylglutaryl-CoA reductase 1.924533 0.03145288 SGEF Src homology 3 domain-containing guanine 1.924356 0.02658412 nucleotide exchange factor KIAA074 KIAA0748 1.923943 0.00099504

GPD2 glycerol-3 -phosphate dehydrogenase 2 1.923915 0.02166602 (mitochondrial) DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PRAME Preferentially expressed antigen in melanoma 1.923708 0.03028361 DFNA5 deafness, autosomal dominant 5 1.923557 0.01859714 ZNF764 zinc finger protein 764 1.92335 0.01449098 VPS13C vacuolar protein sorting 13 homolog C (S. 1.923146 0.0079469 cerevisiae) FAT4 FAT tumor suppressor homolog 4 (Drosophila) 1.922318 0.02481653 COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.921458 0.01957612 ABLIM2 #N/A 1.920353 0.04876135 IL11RA interleukin 11 receptor, alpha 1.919985 0.01904984 PPP2R3A protein phosphatase 2 (formerly 2A), regulatory .919842 0.04499205 subunit B", alpha CNN3 calponin 3, acidic 1.919589 0.01326361 GNE glucosamine (UDP-N-acetyl)-2-epimerase/N- 1.919289 0.01680644 acetylmannosamine kinase DPY19L3 dpy-19-like 3 (C. elegans) 1.919167 0.01045808 LRP12 #N/A 1.9191 16 0.01579065 EP400 E1A binding protein p400 1.918726 0.01295417 ZNF782 zinc finger protein 782 1.917801 0.04972236 SLC9A9 Solute carrier family 9 (sodium/hydrogen 1.917704 0.02162075 exchanger), member 9 C8orf82 chromosome 8 open reading frame 82 1.917694 0.03256964 EEF2 eukaryotic elongation factor-2 kinase 1.917587 0.00471823 CLN3 ceroid-lipofuscinosis, neuronal 3 1.916668 0.01064925 NEDD4L Neural precursor cell expressed, developmentally 1.916554 0.03460953 down-regulated 4-like CLDN11 #N/A 1.91655 0.00517708 TAS1R1 taste receptor, type 1, member 1 1.916462 0.02473007 MCOLN3 mucolipin 3 1.916366 0.04747661 KRT85 #N/A 1.916104 0.01633036 NRDl nardilysin (N-arginine dibasic convertase) 1.915686 0.00426155 LMBR1L limb region 1 homolog (mouse)-like 1.915079 0.00394172 NPTN neuroplastin 1.914001 0.03145238 ZFYVE21 zinc finger, FYVE domain containing 2 1 1.913658 0.04051534 C1QTNF6 Clq and tumor necrosis factor related protein 6 1.913538 0.03897987 KIF13A kinesin family member 13A 1.913366 0.02177671 PIAS3 protein inhibitor of activated STAT, 3 1.912841 0.01839942 ZNF767 zinc finger family member 767 1.911872 0.02293369 BRWD2 Bromodomain and WD repeat domain containing 1.91 1198 0.0221 1182 2 FTSJ3 FtsJ homolog 3 (E. coli) 1.910659 0.0455875 LMBR1 limb region 1 homolog (mouse) 1.909391 0.03414052 KAT2B K(lysine) acetyltransferase 2B 1.909382 0.04214866 NODI nucleotide-binding oligomerization domain 1.909185 0.02204213 containing 1 CTSB cathepsin B 1.909121 0.0417279 THBD #N/A 1.908547 0.03756521 TLE1 transducin-like enhancer of split 1 (E(spl) 1.908 1 8 0.04074464 homolog, Drosophila) PCOLCE2 procollagen C-endopeptidase enhancer 2 1.90722 0.00629512 HERPUD HERPUD family member 2 1.906892 0.02572507 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 2 BAZ2B bromodomain adjacent to zinc finger domain, 2B 1.906596 0.03547602 OSGEP O-sialoglycoprotein endopeptidase 1.906341 0.02084514 FM03 flavin containing monooxygenase 3 1.906176 0.04859884 STRADB STE20-related kinase adaptor beta 1.906072 0.0150799 PNPLA4 patatin-like phospholipase domain containing 4 1.905541 0.04312986 CNOT2 CCR4-NOT transcription complex, subunit 2 1.90473 0.03898023 XRCC6B XRCC6 binding protein 1 1.90444 0.04717261 PI IQSEC1 IQ motif and Sec7 domain 1 1.903414 0.02704439 YRDC yrdC domain containing (E. coli) 1.90296 0.00382355 C15orf39 chromosome 15 open reading frame 39 1.902875 0.00696556 C20orfl2 chromosome 20 open reading frame 12 1.90269 0.00583575 APBB2 amyloid beta (A4) precursor protein-binding, 1.90255 0.03919277 family B, member 2 CCDC138 coiled-coil domain containing 138 1.902246 0.02695231 FAM117B family with sequence similarity 117, member B 1.901772 0.01897273 P2RY6 #N/A 1.901728 0.01023842 ACAA1 #N/A 1.901316 0.01060867 BBX bobby sox homolog (Drosophila) 1.900909 0.01500846 PAXIP1 PAX interacting (with transcription-activation 1.900506 0.03772507 domain) protein 1 TRIO triple functional domain (PTPRF interacting) 1.899678 0.00631 13 HPS5 Hermansky-Pudlak syndrome 5 1.899503 0.00150148 PLK2 polo-like kinase 2 (Drosophila) 1.89847 0.02392197 MYBBP1 MYB binding protein (PI 60) l 1.897963 0.01696392 A SDR42E1 #N/A 1.897472 0.0275267 GMDS GDP-mannose 4,6-dehydratase 1.89713 0.00751708 KIF16B kinesin family member 16B 1.896905 0.02455102 PHF12 #N/A 1.896855 0.04395523 ZNF565 #N/A 1.896339 0.01266803 SLC6A13 solute carrier family 6 (neurotransmitter 1.896275 0.04426482 transporter, GABA), member 13 FAM57A family with sequence similarity 57, member A 1.895465 0.00415853 FAM115A family with sequence similarity 115, member A 1.895377 0.02770417 DVL2 dishevelled, dsh homolog 2 (Drosophila) 1.895338 0.01917641 THTPA #N/A 1.89522 0.01954414 TIMP3 TIMP metallopeptidase inhibitor 3 1.895168 0.04628139 CHM choroideremia (Rab escort protein 1) 1.894444 0.0046574 TESSP2 Testis serine protease 2 1.893707 0.02721581 UROC1 urocanase domain containing 1 1.893215 0.00237883 RNASEN ribonuclease type III, nuclear 1.892763 0.01417458 GPR98 G protein-coupled receptor 98 1.892624 0.01326612 RPL22 ribosomal protein L22 1.892541 0.00202954 COL27A1 collagen, type XXVII, alpha 1 1.892027 0.03196172 IQGAP1 IQ motif containing GTPase activating protein 1 1.891881 0.04620746 GNAZ guanine nucleotide binding protein (G protein), 1.890976 0.03305613 alpha z polypeptide PCTK3 PCTAIRE protein kinase 3 1.889217 0.04404937 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CACNG4 #N/A 1.888787 0.04519699 C14orfl79 chromosome 4 open reading frame 179 1.888348 0.04330074 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 1.888307 0.02252546 APAF1 apoptotic peptidase activating factor 1 1.887923 0.02230552 CBX4 chromobox homolog 4 (Pc class homolog, 1.887855 0.04890595 Drosophila) ZNF544 zinc finger protein 544 1.887464 0.03641561 SMOC1 SPARC related modular calcium binding 1 .88737 0.02939271 RASGEF1 RasGEF domain family, member 1A 1.8871 56 0.03052987 A DCTD dCMP deaminase 1.887005 0.0238736 MAST2 microtubule associated serine/threonine kinase 2 1.886936 0.0432921 SLIT2 slit homolog 2 (Drosophila) 1.88609 0.01870651 FGD5 FYVE, RhoGEF and PH domain containing 5 1.886022 0.00617006 MBOAT1 membrane bound O-acyltransferase domain 1.886004 0.04598058 containing 1 DNAJC13 DnaJ (Hsp40) homolog, subfamily C, member 13 1.885103 0.00977761 MET met proto-oncogene (hepatocyte growth factor 1.884783 0.02601866 receptor) ALKBH8 alkB, alkylation repair homolog 8 (E. coli) 1.883827 0.03014588 FADS2 Fatty acid desaturase 2 1.883525 0.0107778 RBM5 RNA binding motif protein 5 1.882901 0.00067389 ZNF266 zinc finger protein 266 1.882654 0.01663134 ARMC10 armadillo repeat containing 10 1.881877 0.00093444 RNF4 ring finger protein 4 1.881628 0.00674585 PCNX pecanex homolog (Drosophila) 1.880739 0.0295066 MEG 11 multiple EGF-like-domains 11 1.880138 0.00593701 DGKD diacylglycerol kinase, delta 130kDa 1.879797 0.01825987 SFRS8 splicing factor, arginine/serine-rich 8 (suppressor- 1.879646 0.03974937 of-white-apricot homolog, Drosophila) DNTTIP1 deoxynucleotidyltransferase, terminal, interacting 1.87932 0.0331851 protein 1 C16orf70 chromosome 16 open reading frame 70 1.878726 0.04099413 NCRNAO non-protein coding RNA 105 1.878536 0.00912885 0105 SMYD3 SET and MYND domain containing 3 1.877778 0.039881 87 KRTAP5- Keratin associated protein 5-9 1.877195 0.0195685 9 ATP6V1B ATPase, H+ transporting, lysosomal 56/58kDa, 1.8771 07 0.02190657 1 VI subunit l CCDC1 14 coiled-coil domain containing 14 1.876977 0.00807659 VEGFA vascular endothelial growth factor A 1.876933 0.03850214 PAIP1 poly(A) binding protein interacting protein 1 1.876158 0.0161617 COL15A1 collagen, type XV, alpha 1 1.875908 0.03575299 MIF4GD MIF4G domain containing 1.87574 0.04359308 EIF4G1 eukaryotic translation initiation factor 4 gamma, 1 1.874885 0.03844546 BLM Bloom syndrome, RecQ helicase-like 1.874742 0.03470524 SGK196 protein kinase-like protein SgKl 96 1.87418 0.02399226 HSD1 1B2 hydroxysteroid ( -beta) dehydrogenase 2 1.873772 0.019067 MRPS27 Mitochondrial ribosomal protein S27 1.873698 0.03964852 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value GPR137B G protein-coupled receptor 137B 1.872329 0.046985 15 MANBA mannosidase, beta A, lysosomal .872158 0.02873341 LY6G5B #N/A 1.871825 0.03504443 AGXT2L2 alanine-glyoxylate aminotransferase 2-like 2 1.871678 0.01 131574 RH3 histamine receptor H3 1.871571 0.03851706 ACTR8 ARP8 actin-related protein 8 homolog (yeast) 1.87 1091 0.024726 16 FAM82A2 family with sequence similarity 82, member A2 1.870417 0.00217246 SYNE2 spectrin repeat containing, nuclear envelope 2 1.870394 0.01818784 OCRL oculocerebrorenal syndrome of Lowe 1.869419 0.01895175 CRYGA #N/A 1.869382 0.01865733 ACAD 11 acyl-CoA dehydrogenase family, member 11 1.868666 0.04806959 ZKSCAN zinc finger with KRAB and SCAN domains 3 1.867916 0.00078552 3 GALNT11 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.867621 0.03529265 N-acetylgalactosaminyltransferase 11 (GalNAc- Tl l ) PTPN3 protein tyrosine phosphatase, non-receptor type 3 1.867552 0.0341 073 1 CDC42BP CDC42 binding protein kinase alpha (DMPK-like) 1.867402 0.0258652 A IGHG1 Immunoglobulin heavy constant gamma 1 (Glm 1.86731 1 0.03631848 marker) VAV3 vav 3 guanine nucleotide exchange factor 1.86696 0.01798735 STEAP3 STEAP family member 3 1.8661 0.00278677 ST5 suppression of tumorigenicity 5 1.865484 0.02806159 WWP1 WW domain containing E3 ubiquitin protein 1.865067 0.03347901 ligase 1 C9orf93 chromosome 9 open reading frame 93 1.864745 0.00700856 MTR 5-methyltetrahydrofolate-homocysteine 1.864588 0.02616119 methyltransferase ZNF509 Zinc finger protein 509 1.86424 0.04624603 C14orfi02 chromosome 14 open reading frame 102 1.864093 0.001 10785 CAT catalase 1.863965 0.02233098 SORT1 sortilin 1 1.863904 0.00679365 GAL3ST2 galactose-3-O-sulfotransferase 2 1.863453 0.03871831 WDFY3 WD repeat and FYVE domain containing 3 .862532 0.02303744 OR2T3 Olfactory receptor, family 2, subfamily T, member 1.862085 0.03 18299 3 GTF2H4 general transcription factor IIH, polypeptide 4, 1.86 83 0.032341 3 52kDa CCDC23 coiled-coil domain containing 23 1.861564 0.03409132 ADCY9 adenylate cyclase 9 1.86108 0.00469599 POLE polymerase (DNA directed), epsilon 1.860575 0.0261064 DDX50 DEAD (Asp-Glu- Ala-Asp) box polypeptide 50 1.860454 0.04904022 TRAPPC9 #N/A 1.859816 0.02729074 SORBS1 Sorbin and SH3 domain containing 1 1.859486 0.0292001 8 FRMD3 FERM domain containing 3 1.85812 0.03794642 DDX28 #N/A 1.85746 0.00748255 HTT huntingtin 1.857258 0.00520267 POMT2 protein-O-mannosyltransferase 2 1.856647 0.03166017 HSD17B8 hydroxysteroid (17-beta) dehydrogenase 8 1.856477 0.0175483 1/ 6943 7516.1 Supplemental Table 2 Gene Transcripts TJpregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ALPP alkaline phosphatase, placental (Regan isozyme) 1.855804 0.01259775 SERPINB serpin peptidase inhibitor, clade B (ovalbumin), 1.855648 0.03528406 1 member 1 TTC28 tetratricopeptide repeat domain 28 1.854215 0.02108348 FAM86B1 family with sequence similarity 86, member B 1.854169 0.0460832 GUCY1B guanylate cyclase 1, soluble, beta 2 1.854083 0.0275397 2 ACTR1A ARP1 actin-related protein 1 homolog A, 1.853348 0.03328455 centractin alpha (yeast) TLR5 toll-like receptor 5 1.853333 0.03051 119 BRCC3 BRCAl/BRCA2-containing complex, subunit 3 1.852606 0.03453754 HIATI hippocampus abundant transcript 1 1.852532 0.0176408 ARMCX6 armadillo repeat containing, X-linked 6 1.852514 0.03240179 NBR1 neighbor of BRCA1 gene 1 1.852291 0.04358667 TNIK TRAF2 and NCK interacting kinase 1.852078 0.03009865 ALCAM activated leukocyte cell adhesion molecule 1.851831 0.00018223 ITPRIPL1 #N/A 1.851726 0.01392265 ESRP2 epithelial splicing regulatory protein 2 1.85125 0.00626719 ATP1A2 ATPase, Na+/K+ transporting, alpha 2 polypeptide 1.851162 0.04430596 ACP2 acid phosphatase 2, lysosomal 1.851041 0.00870894 MED12L mediator complex subunit 12-like 1.850755 0.01680082 RBM47 RNA binding motif protein 47 1.850449 0.01839222 IL2RB interleukin 2 receptor, beta 1.85013 0.02832439 RNF135 ring finger protein 135 1.849442 0.01864435 PHIP Pleckstrin homology domain interacting protein 1.849173 0.04670099 TYW1 tRNA-yW synthesizing protein 1 homolog (S. 1.84902 0.0295001 cerevisiae) CCDC83 coiled-coil domain containing 83 1.848439 0.00716519 KIAA074 KIAA0746 protein 1.848377 0.04864065 6 1-Sep #N/A 1.848267 0.04618615 MOV10L MovlOll, Moloney leukemia virus 10-like 1, 1.848163 0.02783992 1 homolog (mouse) GSTM4 glutathione S-transferase u 4 1.84803 0.00686783 KIF12 kinesin family member 2 1.847663 0.01009945 PLAGL1 pleiomorphic adenoma gene-like 1 1.847369 0.03548168 CAPN1 calpain 1, (mu/I) large subunit 1.846754 0.04642925 OBFC1 oligonucleotide/oligosaccharide-binding fold 1.846418 0.0466534 containing 1 IFT172 intraflagellar transport 172 homolog 1.846383 0.03441771 (Chlamydomonas) AGL amylo-alpha-1, 6-glucosidase, 4-alpha- 1.846345 0.02053249 glucanotransferase CENPT centromere protein T 1.845845 0.00201983 EPB49 erythrocyte membrane protein band 4.9 (dematin) 1.845428 0.00956853 TLR9 toll-like receptor 9 1.845098 0.02451265 HOXC10 #N/A 1.844827 0.04141346 LIN54 lin-54 homolog (C. elegans) 1.84481 1 0.02042053 ATAD3C ATPase family, AAA domain containing C 1.844768 0.03050448 ACP6 acid phosphatase 6, lysophosphatidic 1.844688 0.02891276 DB1/ 694375I6.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ASAP3 ArfGAP with SH3 domain, ankyrin repeat and PH 1.84451 0.03401894 domain 3 WNK2 WNK lysine deficient protein kinase 2 1.843708 0.00016938 ITGAV integrin, alpha V (vitronectin receptor, alpha 1.842934 0.04834292 polypeptide, antigen CD51) HTRA2 HtrA serine peptidase 2 1.842614 0.04774984 FBN2 fibrillin 2 1.841767 0.01227486 TM9SF4 transmembrane 9 superfamily protein member 4 1.841715 0.01879455 F2RL2 #N/A 1.841701 0.04986855 CSTF2 cleavage stimulation factor, 3' pre-RNA, subunit 2, 1.841567 0.02747869 64kDa HHAT hedgehog acyltransferase 1.839619 0.02416417 FOXF2 forkhead box F2 1.839498 0.0081 1451 TNKS2 tankyrase, TRF1 -interacting ankyrin-related ADP- 1.839248 0.04496397 ribose polymerase 2 RILPL2 Rab interacting lysosomal protein-like 2 1.838902 0.00996151 C19orfl5 Chromosome 19 open reading frame 15 1.838587 0.04290152 FAM125A #N/A 1.837462 0.00701827 FAM73A family with sequence similarity 73, member A 1.83721 0.02226641 CPSF3L cleavage and polyadenylation specific factor 3-like 1.837104 0.02063626 IQCK IQ motif containing K 1.836879 0.01496829 GNA14 #N/A 1.836489 0.01469786 RALGPS1 Ral GEF with PH domain and SH3 binding motif 1.836329 0.01923287 1 DBT dihydrolipoamide branched chain transacylase E2 1.836241 0.01951718 NAV2 neuron navigator 2 1.835983 0.04928384 MITF microphthalmia-associated transcription factor 1.835952 0.03068625 ELL2 elongation factor, RNA polymerase II, 2 1.835366 0.02073358 SCNN1B sodium channel, nonvoltage-gated 1, beta 1.835334 0.01750623 FZD7 #N/A 1.83521 0.01 15498 MAPK12 mitogen-activated protein kinase 12 1.835192 0.02403095 IGSF10 immunoglobulin superfamily, member 0 1.835125 0.01577639 GPATCH G patch domain containing 4 1.834496 0.00899436 4 SMPD4 sphingomyelin phosphodiesterase 4, neutral 1.834372 0.00439255 membrane (neutral sphingomyelinase-3) B4GALT2 UDP-Gal:betaGlcNAc beta 1,4- 1.8338 0.00400978 galactosyltransferase, polypeptide 2 TMEM39 transmembrane protein 39A 1.833209 0.02356189 A PPP2R2C protein phosphatase 2, regulatory subunit B, 1.833122 0.00845584 gamma MYBPH myosin binding protein H 1.833019 0.00486753 BBS1 Bardet-Biedl syndrome 1 1.8329 0.045751 LOCIOOI #N/A 1.832811 0.00342114 30131 AHCY adenosylhomocysteinase 1.832479 0.02432264 EXOSC10 exosome component 10 1.832263 0.04306411 GJC2 gap junction protein, gamma 2, 47kDa 1.832077 0.03543578 AHCTF1 AT hook containing transcription factor 1 1.83198 0.03735963 1/6943751 . 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value GSN gelsolin 1.831593 0.04413044 ATR attractin 1.831417 0.0236229 R F44 Ring finger protein 44 1.831055 0.03914601 PFN2 profilin 2 1.83014 0.02326769 LRLE1 liver-related low express protein 1 1.829773 0.02418802 GIT2 G protein-coupled receptor kinase interacting 1.82951 1 0.0311222 ArfGAP 2 ΓΝΡΡ4Α inositol polyphosphate-4-phosphatase, type I, 1.828306 0.03231606 107kDa SSBP4 single stranded DNA binding protein 4 1.827991 0.0091075 KLK 1 kallikrein-related peptidase 14 1.827705 0.03124541 RTN2 #N/A 1.827064 0.01318014 CISH cytokine inducible SH2-containing protein 1.827041 0.03183502 CLSTN2 calsyntenin 2 1.826481 0.0373253 C9orf3 Chromosome 9 open reading frame 3 1.826206 0.02088969 RORA RAR-related orphan receptor A 1.825839 0.01004205 ZNF692 zinc finger protein 692 1.8258 0.04823366 PAN2 PAN2 poly(A) specific ribonuclease subunit 1.825211 0.03779317 homolog (S. cerevisiae) IFIH1 interferon induced with helicase C domain 1 1.824823 0.04845467 GPN1 GPN-loop GTPase 1 1.823987 0.03073224 SIPA1L1 signal-induced proliferation-associated 1 like 1 1.823875 0.0169873 RI T1 RAD50 interactor 1 1.82387 0.039958 RGS20 regulator of G-protein signaling 20 1.82288 0.02277215 ZNF236 zinc finger protein 236 1.822775 0.04724938 PHF14 PHD finger protein 14 1.822563 0.03727438 KIF2C kinesin family member 2C 1.82231 0.018931 PLEC1 Plectin 1, intermediate filament binding protein 1.821867 0.04362901 500kDa SLC20A1 solute carrier family 20 (phosphate transporter), 1.821633 0.01516049 member 1 CNOT8 CCR4-NOT transcription complex, subunit 8 1.821 121 0.02498699 RAP1GD RAP1, GTP-GDP dissociation stimulator 1 1.819878 0.01679424 ¾ 1 SACM1L SACl suppressor of actin mutations 1-like (yeast) 1.819681 0.00093656 SMG5 Smg-5 homolog, nonsense mediated mRNA decay 1.819608 0.01248203 factor (C. elegans) CADPS Ca++-dependent secretion activator 1.819099 0.01745439 CLYBL citrate lyase beta like 1.819068 0.03252962 SCCPDH saccharopine dehydrogenase (putative) 1.818406 1.08E-05 METRNL meteorin, glial cell differentiation regulator-like 1.817181 0.02789795 CAMKK2 calcium/calmodulin-dependent protein kinase 1.817056 0.02728463 kinase 2, beta MCM3AP minichromosome maintenance complex 1.816833 0.01036449 component 3 associated protein URG4 Up-regulated gene 4 1.816744 0.03609274 ULK2 unc-51-like kinase 2 (C. elegans) 1.816684 0.01404583 STAB1 stabilin 1 1.816028 0.03390585 KDELC1 KDEL (Lys-Asp-Glu-Leu) containing 1 1.815854 0.03640204 EHHADH enoyl-CoA, hydratase/3 -hydroxy acyl CoA 1.815128 0.01072486 Bl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value dehydrogenase GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.814714 0.02678242 ARSB arylsulfatase B 1.814591 0.0476001 TTL tubulin tyrosine ligase 1.814429 0.02900906 CDC23 Cell division cycle 23 homo log (S. cerevisiae) 1.814312 0.01424556 NLN neurolysin (metallopeptidase M3 family) 1.814047 0.00363452 CDKN2A #N/A 1.813664 0.00782587 SEC14L5 SEC14-like 5 (S. cerevisiae) 1.813525 0.00778707 LOC1584 #N/A 1.813506 0.02379264 35 RNF160 ring finger protein 160 1.81331 0.01364145 VPS13B vacuolar protein sorting 13 homolog B (yeast) 1.813221 0.02323946 AXL AXL receptor tyrosine kinase 1.812906 0.01483759 C2orfl6 chromosome 2 open reading frame 16 1.812404 0.00257035 DI030S #N/A 1.812199 0.02990504 DRG2 developmentally regulated GTP binding protein 2 1.812069 0.01854784 XAB2 XPA binding protein 2 1.811657 0.02446796 XP07 exportin 7 1.81 1431 0.02173881 DOCK5 dedicator of cytokinesis 5 1.81 1424 0.03101188 ZSCAN16 zinc finger and SCAN domain containing 16 1.810978 0.02805285 GSDMA #N/A 1.810932 0.04439628 KIAA031 KIAA0319 1.810581 0.04796698 9 PCCB propionyl CoA carboxylase, beta polypeptide 1.81017 0.03327504 DARS2 aspartyl-tRNA synthetase 2, mitochondrial 1.809934 0.0004163 ZNRF4 #N/A 1.809753 0.0418607 NOL6 nucleolar protein family 6 (RNA-associated) 1.809392 0.01903122 BAIAP3 BAI1-associated protein 3 1.808624 0.02837442 SLC25A1 solute carrier family 25 (mitochondrial carrier, 1.808516 0.04836052 2 Aralar), member 12 UFSP2 #N/A 1.808457 0.02242258 ABO #N/A 1.808305 0.01404044 C17orf58 chromosome 17 open reading frame 58 1.808026 0.00737566 CERCAM cerebral endothelial cell adhesion molecule 1.807599 0.04245661 FNDC3B fibronectin type III domain containing 3B 1.807337 0.04828007 LPHN1 latrophilin 1 1.807313 0.03455603 STOX1 storkhead box 1 1.807307 0.04072721 HPS3 Hermansky-Pudlak syndrome 3 1.806824 0.00162527 ACAD9 acyl-CoA dehydrogenase family, member 9 1.806784 0.0371985 C2 complement component 2 1.80667 0.03022582 SLC2A13 solute carrier family 2 (facilitated glucose 1.806614 0.03103435 transporter), member 13 RARS2 arginyl-tRNA synthetase 2, mitochondrial 1.805822 0.00425774 GDPD3 glycerophosphodiester phosphodiesterase domain 1.805808 0.0364083 containing 3 CAMK2G calcium/calmodulin-dependent protein kinase II 1.805609 0.04464108 gamma ZNF641 zinc finger protein 641 1.805397 0.03755286 NFAT5 nuclear factor of activated T-cells 5, toniciry- 1.80533 0.02591485 responsive 1/6943 7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest Symbol Change value RICTOR RPTOR independent companion of MTOR, 1.8052 0.01457283 complex 2 EPB41 erythrocyte membrane protein band 4.1 1.804925 0.02384749 (elliptocytosis 1, RH-linked) TMEM10 transmembrane protein 104 1.80478 0.01729592 4 CD70 #N/A 1.804706 0.02510777 RPS6KA2 ribosomal protein S6 kinase, 90kDa, polypeptide 2 1.804574 0.0184449 SLC39A1 #N/A 1.804555 0.01947493 1 CTSL2 #N/A 1.804045 0.00453175 USP1 1 ubiquitin specific peptidase 11 1.803911 0.01986362 KLHL5 Kelch-like 5 (Drosophila) 1.80375 0.04121789 OPA1 optic atrophy 1 (autosomal dominant) 1.803711 0.03903617 SLC47A2 solute carrier family 47, member 2 1.803291 0.03449051 PKN1 protein kinase l 1.803225 0.02628179 TMTC1 transmembrane and tetratricopeptide repeat 1.802521 0.04406318 containing 1 CLCN6 chloride channel 6 1.802064 0.01008228 TBR1 T-box, brain, 1 1.801 116 0.04777212 EPHB2 EPH receptor B2 1.800882 0.00867104 PUS3 #N/A 1.80086 0.01529983 SHPK sedoheptulokinase 1.800252 0.00027963 OSBPL9 Oxysterol binding protein-like 9 1.799943 0.00284758 KIAA132 KIAA1324 1.799673 0.01824525 4 RBM41 RNA binding motif protein 4 1 1.799437 0.03296399 PITPNM2 phosphatidylinositol transfer protein, membrane- 1.799147 0.03440953 associated 2 STAMBP STAM binding protein-like 1 1.798892 0.04856885 L I PDLIM5 PDZ and LIM domain 5 1.79811 0.01328438 PDDC1 Parkinson disease 7 domain containing 1 1.797687 0.02161418 TTC3 tetratricopeptide repeat domain 3 1.797303 0.02193066 FLJ1 1235 #N/A 1.797278 0.04835643 SERTAD1 #N/A 1.797206 0.03107296 Clorfl44 chromosome 1 open reading frame 144 1.797013 0.00876496 NCAPH non-SMC condensin I complex, subunit H 1.796877 0.02573221 VSIG6 #N/A 1.796635 0.01654433 KIF20A kinesin family member 20A 1.796555 0.00619896 KIAA052 KIAA0528 1.796529 0.04915525

ZNF793 #N/A 1.796318 0.00894016 NOG #N/A 1.796189 0.02642183 COPS7B COP9 constitutive photomorphogenic homolog 1.795644 0.00171403 subunit 7B (Arabidopsis) CYYR1 Cysteine/tyrosine-rich 1 1.795609 0.02061148 ALS2 Amyotrophic lateral sclerosis 2 (juvenile) 1.795276 0.00416629 STK24 serine/threonine kinase 24 (STE20 homolog, 1.794633 0.04565266 yeast) D / 69437516. Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value HDHD2 haloacid dehalogenase-like hydrolase domain 1.794609 0.0439966 containing 2 ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide 1.794504 0.04608723 C17orf57 chromosome 7 open reading frame 57 1.794479 0.00928227 USP4 ubiquitin specific peptidase 4 (proto-oncogene) 1.794435 0.04240151 PPM1M protein phosphatase, Mg2+/Mn2+ dependent, 1M 1.794264 0.03533697 TNFRSF1 Tumor necrosis factor receptor superfamily, 1.794187 0.02680733 9 member 19 NAGK #N/A 1.793923 0.00154956 MKLN1 muskelin 1, intracellular mediator containing kelch 1.793833 0.00447919 motifs ZNF561 zinc finger protein 561 1.793275 0.03392283 PCYT2 phosphate cytidylyltransferase 2, ethanolamine 1.792846 0.01623884 TMEM18 transmembrane protein 185A 1.79283 0.02359851 rA TMIGD1 transmembrane and immunoglobulin domain 1.792592 0.01374157 containing 1 TRIM69 tripartite motif-containing 69 1.792487 0.03262148 RAB3GA RAB3 GTPase activating protein subunit 2 (non- 1.792358 0.04858857 P2 catalytic) ANK1 ankyrin 1, erythrocytic 1.792161 0.048551 1 PRKX protein kinase, X-linked 1.792078 0.02142469 RBM23 #N/A 1.791969 0.0206475 EIF2C4 eukaryotic translation initiation factor 2C, 4 1.791931 0.03041025 C13orfl5 Chromosome 13 open reading frame 15 1.791746 0.0365939 SPDYE7P speedy homolog E7 (Xenopus laevis), pseudogene 1.791364 0.00311628 SLC6A11 solute carrier family 6 (neurotransmitter 1.791296 0.02376178 transporter, GABA), member 11 C3orf75 chromosome 3 open reading frame 75 1.791217 0.04476106 AGK acylglycerol kinase 1.791 188 0.02184074 LIMS2 LIM and senescent cell antigen-like domains 2 1.791155 0.03239708 FAM40A family with sequence similarity 40, member A 1.791 114 0.04260628 BIRC6 baculoviral IAP repeat-containing 6 1.791019 0.04970096 STRN striatin, calmodulin binding protein 1.790869 0.00103203 RBMS1 RNA binding motif, single stranded interacting 1.790598 0.00484691 protein 1 PRKCA protein kinase C, alpha 1.790567 0.02417993 DGCR6L #N/A 1.790378 0.02948803 KCTD8 potassium channel tetramerisation domain 1.789556 0.03121183 containing 8 NFKBIL2 nuclear factor of kappa light polypeptide gene 1.789224 0.01393889 enhancer in B-cells inhibitor-like 2 SHKBP1 SH3KBP1 binding protein 1 1.789197 0.01337287 PCDHB5 protocadherin beta 5 1.788989 0.04106313 POP1 processing of precursor 1, ribonuclease P/MRP 1.788281 0.02037732 subunit (S. cerevisiae) ARFGEF2 ADP-ribosylation factor guanine nucleotide- 1.788048 0.04903073 exchange factor 2 (brefeldin A-inhibited) IL1 1 interleukin 1 1.78803 0.04701437 OR8G5 #N/A 1.78788 0.01935812 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value EIF2C1 eukaryotic translation initiation factor 2C, 1 1.787546 0.03013723 C7orf47 chromosome 7 open reading frame 47 1.787392 0.01406517 LGALS3 lectin, galactoside-binding, soluble, 3 1.786219 0.04531611 ATCAY #N/A 1.785867 0.02441094 CCDC21 coiled-coil domain containing 2 1 1.785799 0.01918401 STX1A syntaxin A (brain) 1.785679 0.02118002 RP4- N/A 1.785668 0.01 19943 692D3.1 SNX25 sorting nexin 25 1.78541 0.02564642 PLCB4 phospholipase C, beta 4 1.78505 0.02860976 WASH2P WAS protein family homolog 2 pseudogene 1.784848 0.00363915 SPARCL1 SPARC-like 1 (hevin) 1.784575 0.00678883 PI4KA phosphatidylinositol 4-kinase, catalytic, alpha 1.78394 0.041 19075 LILRA6 leukocyte immunoglobulin-like receptor, 1.783197 0.0073758 subfamily A (with TM domain), member 6 TMPRSS1 transmembrane protease, serine 1 B 1.782781 0.04890759 IB SH2D4A SH2 domain containing 4A 1.782601 0.00558183 CA3 carbonic anhydrase III, muscle specific 1.782466 0.04586045 ATG16L1 ATG16 autophagy related 16-like 1 (S. cerevisiae) 1.782453 0.02898332 GIGYF2 GRB10 interacting GYF protein 2 1.782209 0.04126325 Clorf57 chromosome 1 open reading frame 57 1.782172 0.03608043 CNTNAP contactin associated protein-like 4 1.782093 0.0035102 4 KPNA6 karyopherin alpha 6 (importin alpha 7) 1.78 923 0.03 10852 HERC5 hect domain and RLD 5 1.78 1794 0.003 17627 PGM2 Phosphoglucomutase 2 1.781686 0.02399861 DGKG diacylglycerol kinase, gamma 90kDa 1.781287 0.01284394 RFC1 replication factor C (activator 1) 1, 145kDa 1.780866 0.03247922 HECTD2 HECT domain containing 2 1.780455 0.00275198 NCRNAO #N/A 1.780057 0.02102031 0153 PER2 period homolog 2 (Drosophila) 1.779887 0.04286856 KIAA171 KIAA1715 1.779871 0.01240973 5 BICD2 bicaudal D homolog 2 (Drosophila) 1.779762 0.0003449 AP1B1 adaptor-related protein complex 1, beta 1 subunit 1.779553 0.01993621 FTSJD2 FtsJ methyltransferase domain containing 2 1.779443 0.04459761 C12orf40 #N/A 1.779386 0.02461062 NOC4L nucleolar complex associated 4 homolog (S. 1.77938 0.00519869 cerevisiae) C9orf72 chromosome 9 open reading frame 72 1.779325 0.001 16813 LASP1 LIM and SH3 protein 1 1.779305 0.02397077 INTS10 integrator complex subunit 10 1.779 159 0.03963764 FHOD1 formin homology 2 domain containing 1 1.778 196 0.01 399849 C8B complement component 8, beta polypeptide 1.778159 0.03169858 C3orf24 chromosome 3 open reading frame 24 1.778132 0.00908447 ZNF621 #N/A 1.778004 0.00522172 WIPI2 WD repeat domain, phosphoinositide interacting 2 1.777875 0.04845 68 DGCR2 DiGeorge syndrome critical region gene 2 1.777194 0.03677183 1/6943 7 16. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PPP2R5A protein phosphatase 2, regulatory subunit B', alpha 1.776972 0.03961713 U C84A Unc-84 homolog A (C. elegans) 1.776587 0.04309932 RTN4 Reticulon 4 1.776363 0.01948926 MIPOL1 mirror-image Polydactyly 1 1.77569 0.03332746 XRCC3 X-ray repair complementing defective repair in 1.775659 0.04521804 Chinese hamster cells 3 ELL elongation factor RNA polymerase II 1.775647 0.02696673 Clorfll4 #N/A 1.775577 0.048981 13 C7orf54 #N/A 1.775088 0.03773488 FGGY FGGY carbohydrate kinase domain containing 1.774808 0.02179662 LVR #N/A 1.774804 0.00064064 KRT6A keratin 6A 1.774477 0.01592729 ATAD3A ATPase family, AAA domain containing 3A 1.774155 0.01641257 CAPN9 calpain 9 1.773901 0.00709331 SRGAP1 SLIT-ROBO Rho GTPase activating protein 1 1.77357 0.01567887 SEC23A Sec23 homolog A (S. cerevisiae) 1.772801 0.02654777 SOX13 SRY (sex determining region Y)-box 13 1.772618 0.04520642 MSL3 male-specific lethal 3 homolog (Drosophila) 1.772485 0.03587881 GBA glucosidase, beta, acid 1.772456 0.02752661 SMG1 SMG1 homolog, phosphatidylinositol 3-kinase- 1.771998 0.01037175 related kinase (C. elegans) PLCB1 phospholipase C, beta 1 (phosphoinositide- 1.771847 0.03330809 specific) NCF1 neutrophil cytosolic factor 1 1.771446 0.00609771 NCAPH2 non-SMC condensin II complex, subunit H2 1.771348 0.00192561 LRCH3 leucine-rich repeats and calponin homology (CH) 1.771288 0.02829728 domain containing 3 BPNT1 #N/A 1.771 126 0.0442052 MPP7 membrane protein, palmitoylated 7 (MAGU p55 1.770808 0.03390227 subfamily member 7) SLC24A1 solute carrier family 24 1.770405 0.01181665 (sodium/potassium/calcium exchanger), member 1 COL19A1 collagen, type XIX, alpha 1 1.769544 0.00758784 CTA- Hypothetical FLJ23584 1.769128 7.63E-06 216E10.6 MGLL monoglyceride lipase 1.769073 0.01765371 DUSP23 dual specificity phosphatase 23 1.769028 0.02176854 DCP1B DCP1 decapping enzyme homolog B (S. 1.768896 0.04886241 cerevisiae) LDB1 LIM domain binding 1 1.768377 0.04418318 TNFRSF2 tumor necrosis factor receptor superfamily, 1.768189 0.0455518 1 member 2 1 RPS6KC1 ribosomal protein S6 kinase, 52kDa, polypeptide 1 1.767957 0.01187031 TARBP1 TAR (HIV-1) RNA binding protein 1 1.76731 0.04997674 JOSD1 Josephin domain containing 1 1.766767 0.04966897 BCAR3 breast cancer anti-estrogen resistance 3 1.766686 0.04741963 UBL4A #N/A 1.766604 0.01994057 KRT28 keratin 8 1.766388 0.0200145 MUC 1 #N/A 1.766316 0.04988542 DNAJC16 DnaJ (Hsp40) homolog, subfamily C, member 16 1.765974 0.00128657 DB / 69437516. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ACOl aconitase 1, soluble 1.765545 0.02519563 CCT6B chaperonin containing TCPl, subunit 6B (zeta 2) 1.765154 0.01441639 ZNF234 zinc finger protein 234 1.764221 0.04129703 WEE1 WEE1 homolog (S. pombe) 1.76422 0.0190755 UGT3A2 UDP glycosyltransferase 3 family, polypeptide A2 1.763886 0.00745899 TKTL2 #N/A 1.763472 0.00224344 GBA2 glucosidase, beta (bile acid) 2 1.76299 0.00583495 MLL5 myeloid/lymphoid or mixed-lineage leukemia 5 1.762872 0.03968122 (trithorax homolog, Drosophila) RBM24 RNA binding motif protein 24 1.762854 0.00083583 ALK anaplastic lymphoma receptor tyrosine kinase 1.762772 0.02290011 AFTPH aftiphilin 1.762753 0.03581729 FGD2 FYVE, RhoGEF and PH domain containing 2 1.762355 0.0043171 1 RETN resistin 1.762318 0.01546848 RB S ribokinase 1.76176 0.04351475 ZFHX4 zinc finger homeobox 4 1.761664 0.02954824 CBLC Cas-Br-M (murine) ecotropic retroviral 1.761662 0.010678 transforming sequence c USHBP1 Usher syndrome 1C binding protein 1 1.761661 0.02372015 MTHFD2 methylenetetrahydrofolate dehydrogenase 1.761655 0.03894478 L ( ADP+ dependent) 2-like KLF4 Kruppel-like factor 4 (gut) 1.761564 0.01640878 BCL6 #N/A 1.76123 0.0286744 NUDCD3 NudC domain containing 3 1.760927 0.0474457 KIAA201 #N/A 1.760852 0.02436456 3 RTN3 reticulon 3 1.760713 0.021 11797 SH2D3C SH2 domain containing C 1.760554 0.00272672 USP39 ubiquitin specific peptidase 39 1.760536 0.03374848 GOLGB1 golgin Bl 1.760309 0.0356427 GPR155 G protein-coupled receptor 155 1.759774 0.01942222 LENG8 Leukocyte receptor cluster (LRC) member 8 1.758963 0.0175276 RICH2 Rho-type GTPase-activating protein RICH2 1.758936 0.04179542 PAPSS1 3'-phosphoadenosine 5'-phosphosulfate synthase 1 1.758882 0.04546671 BMPR2 bone morphogenetic protein receptor, type II 1.758291 0.04976859 (serine/threonine kinase) KIF26B #N/A 1.758279 0.03171182 MAP3K7I Mitogen-activated protein kinase kinase kinase 7 1.758279 0.02067163 P3 interacting protein 3 MLL4 myeloid/lymphoid or mixed-lineage leukemia 4 1.758142 0.00894005 ZNF225 zinc finger protein 225 1.757809 0.03519834 MBNL3 #N/A 1.757298 0.01480562 RAI14 retinoic acid induced 14 1.75729 0.03349575 ATF3 activating transcription factor 3 1.756661 0.0451451 FBX039 #N/A 1.756165 0.00121815 UBQLN4 ubiquilin 4 1.7561 14 0.02382911 FAM105A family with sequence similarity 105, member A 1.756019 0.02698624 B4GALN beta-l,4-N-acetyl-galactosaminyl transferase 3 1.755953 0.02418084 T3 ADAMTS ADAM metallopeptidase with thrombospondin 1.75562 0.04203138 DBl/ 69437516. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 19 type 1 motif, 19 LOC4402 similar to p40 1.755187 0.01646372 58 ZNF184 zinc finger protein 184 1.754955 0.02223986 ZNF445 zinc finger protein 445 1.754923 0.03286542 LRWD1 leucine-rich repeats and WD repeat domain 1.754383 0.01448462 containing 1 G6PD glucose-6-phosphate dehydrogenase 1.753382 0.02781807 TOPBP1 topoisomerase (DNA) II binding protein 1 1.753342 0.04355243 MAGEA5 melanoma antigen family A, 5 1.753252 0.02734386 Clorfl4 chromosome 1 open reading frame 4 1.753243 0.03546329 GSTA4 glutathione S-transferase alpha 4 1.753107 0.00541283 PLXNA3 Plexin A3 1.752528 0.0007546 C3orf52 #N/A 1.752221 0.02216849 SCN5A sodium channel, voltage-gated, type V, alpha 1.752179 0.0255401 1 subunit C22orf9 #N/A 1.752071 0.04045017 SEC14L1 SEC14-like 1 (S. cerevisiae) 1.751624 0.0065086 CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.749697 0.01832449 D3 subunit 3 EIF3D eukaryotic translation initiation factor 3, subunit D 1.749589 0.03090098 DGAT1 diacylglycerol O-acyltransferase homolog 1 1.749071 0.03456439 (mouse) COX4I1 #N/A 1.749039 0.03773461 EVI5 ecotropic viral integration site 5 1.748676 0.01688849 TGFA transforming growth factor, alpha 1.748632 0.03193993 SEMA6A Sema domain, transmembrane domain (TM), and 1.748458 0.01669209 cytoplasmic domain, (semaphorin) 6A ZNF410 zinc finger protein 410 1.748024 0.01204823 NHLH1 #N/A 1.747231 0.03028152 COBLL1 COBL-like 1 1.747195 0.04850633 SLC23A2 solute carrier family 23 (nucleobase transporters), 1.747049 0.04342467 member 2 NPHP4 nephronophthisis 4 1.746754 0.03738345 CSRP2BP CSRP2 binding protein 1.746524 0.02273079 GAB1 GRB2-associated binding protein 1 1.746467 0.03029872 C20orfl32 chromosome 20 open reading frame 132 1.746253 0.035852 DOC2A double C2-like domains, alpha 1.74612 0.02490822 GTPBP2 #N/A 1.745407 0.02223491 ERF #N/A 1.74482 0.02510774 TNKS tankyrase, TRF1 -interacting ankyrin-related ADP- 1.744666 0.04627214 ribose polymerase SEC24D SEC24 family, member D (S. cerevisiae) 1.744358 0.03911211 8-Sep #N/A 1.744145 0.00582905 GMIP GEM interacting protein 1.744115 0.03051 105 EPHA3 EPH receptor A3 1.7441 1 0.02174902 PCDHGB protocadherin gamma subfamily B, 1 1.743643 0.03759205 1 STAT1 signal transducer and activator of transcription 1, 1.74348 0.04240031 91kDa DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value UNC50 unc-50 homolog (C. elegans) 1.743399 0.04456063 MY015A myosin XVA 1.742508 0.03231288 TDRD3 tudor domain containing 3 1.742328 0.04813857 TRIP 13 thyroid hormone receptor interactor 13 1.741503 0.03023358 PIKFYVE phosphoinositide kinase, FYVE finger containing 1.741298 0.0125666 TMEM19 transmembrane protein 192 1.741076 0.02259603 2 AGFG1 ArfGAP with FG repeats 1 1.740148 0.00038148 IGFL4 #N/A 1.73996 0.03696647 RAB24 RAB24, member RAS oncogene family 1.739907 0.01928266 NDUFB11 NADH dehydrogenase (ubiquinone) 1 beta 1.73983 0.02005851 subcomplex, 11, 17.3kDa AB 1L1 #N/A 1.739804 0.03588803 NKRF NFKB repressing factor 1.739686 0.04900439 Cllorf74 #N/A 1.739683 0.02350089 NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1.739642 0.021 14725 1, 75kDa (NADH-coenzyme Q reductase) POU2F1 POU class 2 homeobox 1 1.739423 0.02085693 FAP2 microfibrillar-associated protein 2 1.739182 0.03267798 SEC22C SEC22 vesicle trafficking protein homolog C (S. 1.739063 0.00442219 cerevisiae) ADAM2 ADAM metallopeptidase domain 2 1.738719 0.03982981 MTMR1 myotubularin related protein 1 1.738523 0.01841331 DR1 down-regulator of transcription 1, TBP-binding 1.738386 0.04902791 (negative cofactor 2) EIF2C2 eukaryotic translation initiation factor 2C, 2 1.737381 0.02796271 DUSP3 dual specificity phosphatase 3 1.737377 0.00223923 ABCA2 ATP-binding cassette, sub-family A (ABC1), 1.736876 0.01473507 member 2 STK11IP serine/threonine kinase 11 interacting protein 1.736757 0.02103678 RAB3D RAB3D, member RAS oncogene family 1.736335 0.0302014 CADM4 #N/A 1.73612 0.03829267 CDK5RA CDK5 regulatory subunit associated protein 2 1.735693 0.02311894 P2 COPS5 COP9 constitutive photomorphogenic homolog 1.73531 0.01 165778 subunit 5 (Arabidopsis) TSC2 tuberous sclerosis 2 1.735243 0.04697442 PAX6 paired box 6 1.735007 5.01E-06 NVL nuclear VCP-like 1.734827 0.00569968 C19orf44 chromosome 19 open reading frame 44 1.734504 0.04317116 TTC39B tetratricopeptide repeat domain 39B 1.73421 1 0.04698457 TRAPPC1 #N/A 1.733987 0.0281 1378 0 DCHS2 dachsous 2 (Drosophila) 1.733625 0.03898632 ZBTB2 zinc finger and BTB domain containing 2 1.733558 0.02724021 LCA5 Leber congenital amaurosis 5 1.733514 0.01777422 FBXL17 F-box and leucine-rich repeat protein 17 1.733476 0.02285153 SFXN5 sideroflexin 5 1.733428 0.00361959 PEX26 peroxisomal biogenesis factor 26 1.733322 6.10E-05 RAB3IP RAB3A interacting protein (rabin3) 1.73291 0.03062512 1/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value BCL9 B-cell CLL/lymphoma 9 1.732645 0.01 182714 SORD sorbitol dehydrogenase 1.732637 0.00609886 KDM5B lysine (K)-specific demethylase 5B 1.732628 0.04388569 MFSD3 major facilitator superfamily domain containing 3 1.732624 0.00186089 LRRC1 Leucine rich repeat containing 1 1.732577 0.01498779 G6PC2 #N/A 1.732403 0.02479933 TRAM2 translocation associated membrane protein 2 1.731537 0.0246794 PTK2 PT 2 protein tyrosine kinase 2 1.731098 0.03442737 RRP12 ribosomal RNA processing 12 homolog (S. 1.730868 0.01376982 cerevisiae) PPARG peroxisome proliferator-activated receptor gamma 1.730854 0.02459021 KLC2 Kinesin light chain 2 1.730599 0.03664663 SLC19A1 solute carrier family 9 (folate transporter), 1.730571 0.01485065 member 1 LPCAT3 lysophosphatidylcholine acyltransferase 3 1.729979 0.04133057 ARHGEF Rho guanine nucleotide exchange factor (GEF) 3 1.729836 0.04145086 3 ACACA acetyl-CoA carboxylase alpha 1.729759 0.04237568 NUP210 nucleoporin 2 1OkDa 1.729416 0.04084509 ANKMY1 ankyrin repeat and MYND domain containing 1 1.729163 0.0270179 OGT O-linked N-acetylglucosamine (GlcNAc) 1.728718 0.04340233 transferase (UDP-N- acetylglucosamine:polypeptide-N- acetylglucosaminyl transferase) S100A9 #N/A 1.728669 0.00818468 RBM22 RNA binding motif protein 22 1.728626 0.01614761 ITSN2 intersectin 2 1.726993 0.04145017 OS9 osteosarcoma amplified 9, endoplasmic reticulum 1.725916 0.01749409 lectin FAM38A family with sequence similarity 38, member A 1.72533 0.0335846 PIK3R1 phosphoinositide-3 -kinase, regulatory subunit 1 1.724967 0.04257376 (alpha) PCCA propionyl CoA carboxylase, alpha polypeptide 1.724233 0.01410244 DOCK9 dedicator of cytokinesis 9 1.724079 0.02135059 GABRG3 gamma-aminobutyric acid (GABA) A receptor, 1.724029 0.03300689 gamma 3 DEFA5 defensin, alpha 5, Paneth cell-specific 1.723663 0.00578865 NOTCH3 Notch homolog 3 (Drosophila) 1.723621 0.03672981 CPEB2 cytoplasmic polyadenylation element binding 1.723351 0.00139721 protein 2 HECTD1 HECT domain containing 1 1.723184 0.04818697 PLXNC1 plexin CI 1.723158 0.01013153 ABCA4 ATP-binding cassette, sub-family A (ABC1), 1.722941 0.04232054 member 4 DCC #N/A 1.722929 0.00956524 LAMC1 laminin, gamma 1 (formerly LAMB2) 1.722821 0.02734652 OPN3 opsin 3 1.722424 0.03608216 KATNAL #N/A 1.722216 0.01175097 1 HOXC8 homeobox C8 1.721862 0.04974292 / 694375 16.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value NFXL1 Nuclear transcription factor, X-box binding-like 1 1.721555 0.02761823 PORCN porcupine homolog (Drosophila) 1.721067 0.04807794 APTX Aprataxin 1.720781 0.04496039 PLEKHM pleckstrin homology domain containing, family M 1.720765 0.04294087 2 (with RUN domain) member 2 MYO myosin X 1.72049 0.03749112 GRK6 G protein-coupled receptor kinase 6 1.71984 0.03663987 SSH2 slingshot homolog 2 (Drosophila) 1.719656 0.03325557 VAMP4 vesicle-associated membrane protein 4 1.719461 0.02416613 CRISPLD cysteine-rich secretory protein LCCL domain 1.719216 0.01 156081 2 containing 2 ANXAl annexin A l 1.719177 0.04489786 DMC1 DMC1 dosage suppressor of mckt homolog, 1.719172 0.00216327 meiosis-specific homologous recombination (yeast) NCOA2 nuclear receptor coactivator 2 1.71912 0.01425815 DUSP22 dual specificity phosphatase 22 1.718997 0.02891459 PRCC papillary renal cell carcinoma (translocation- 1.718941 0.04542483 associated) COL4A5 collagen, type IV, alpha 5 1.718934 0.03131216 LONRF2 LON peptidase N-terminal domain and ring finger 1.718819 0.01 141586 2 COX4I2 #N/A 1.718641 0.03059842 SLC9A2 solute carrier family 9 (sodium/hydrogen 1.718166 0.02822742 exchanger), member 2 EXOG endo/exonuclease (5'-3'), endonuclease G-Iike 1.717836 0.02194731 C12orf60 #N/A 1.71779 0.0298019 C5orf30 chromosome 5 open reading frame 30 1.717496 0.033414 COL21A1 collagen, type XXI, alpha 1 1.717491 0.00862176 HAS3 #N/A 1.717446 0.04575845 BAI1 brain-specific angiogenesis inhibitor 1 1.717373 0.00815145 RERE arginine-glutamic acid dipeptide (RE) repeats 1.71735 0.0138092 WHSC1 Wolf-Hirschhorn syndrome candidate 1 1.717052 0.03095402 HERC2 hect domain and RLD 2 1.717048 0.03923331 PCSK6 proprotein convertase subtilisin/kexin type 6 1.716871 0.03369358 CEP97 centrosomal protein 97kDa 1.716708 0.01188736 MRPL55 Mitochondrial ribosomal protein L55 1.71648 0.03894057 HARS2 histidyl-tRNA synthetase 2, mitochondrial 1.715719 0.03591061 (putative) SLC35B2 solute carrier family 35, member B2 1.715575 0.03768911 KIAA130 Raptor 1.715481 0.01002851 3 DNAJB5 DnaJ (Hsp40) homolog, subfamily B, member 5 1.71473 0.02289742 CCDC91 coiled-coil domain containing 9 1 1.71455 0.00648879 DE ND5 DENN/MADD domain containing 5B .714332 0.02185475 B PSMD14 proteasome (prosome, macropain) 26S subunit, 1.713989 0.02500735 non-ATPase, 4 IRF6 interferon regulatory factor 6 1.7131 18 0.0205667 GPATCH G patch domain containing 1 1.712933 0.04344977 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 1 AJAP1 adherens junctions associated protein 1 1.712712 0.01253223 PCNXL2 Pecanex-like 2 (Drosophila) 1.712481 0.04600786 MAP4K4 mitogen-activated protein kinase kinase kinase 1.712186 0.04245277 kinase 4 TOX2 TOX high mobility group box family member 2 1.712142 0.01986638 CDK5 #N/A 1.712097 0.04453054 GPRC5C #N/A 1.71 1964 0.01376975 B9D2 #N/A 1.71 1881 0.03348781 RPS6KA1 ribosomal protein S6 kinase, 90kDa, polypeptide 1 1.71 1861 0.02549594 MYH6 myosin, heavy chain 6, cardiac muscle, alpha 1.71 1724 0.01693347 CETP #N/A 1.710863 0.01956263 ATP8B1 ATPase, aminophospholipid transporter, class I, 1.710738 0.02400154 type 8B, member 1 COQ7 coenzyme Q7 homolog, ubiquinone (yeast) 1.710519 0.02874881 ZNF202 #N/A 1.71042 0.01387536 MAP4K3 mitogen-activated protein kinase kinase kinase 1.710348 0.0179431 1 kinase 3 TPRG1L tumor protein p63 regulated 1-like 1.709752 0.02459877 FBXL2 F-box and leucine-rich repeat protein 2 1.70972 0.04192718 SI sucrase-isomaltase (alpha-glucosidase) 1.709514 0.04940818 GRIN1 #N/A 1.709203 0.04015842 MY019 #N/A 1.709143 0.022694 SPOCD1 SPOC domain containing 1 1.709134 0.04237795 LPIN2 lipin 2 1.708429 0.00705372 MED 8 mediator complex subunit 8 1.708003 0.00678397 AP2A2 adaptor-related protein complex 2, alpha 2 subunit 1.707895 0.01275162 ADAMTS ADAMTS -like 4 1.70756 0.00646457 L4 HCFC1 host cell factor C (VP16-accessory protein) .707475 0.0240554 GALNT7 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.707402 0.0173733 1 N-acetylgalactosaminyltransferase 7 (GalNAc-T7) FNIP1 Folliculin interacting protein 1 1.707247 0.04196063 YTHDC2 YTH domain containing 2 1.707026 0.03883546 GRHL2 grainyhead-like 2 (Drosophila) 1.706873 0.02848341 GGCX gamma-glutamyl carboxylase 1.706652 0.04784631 SLC05A1 #N/A 1.706296 0.0130894 HIST1H3 #N/A 1.706099 0.02187137 H POMT1 protein-O-mannosyltransferase 1 1.705442 0.03660587 SYT12 synaptotagmin XII 1.705407 0.04558376 FLJ41423 hypothetical LOC399886 1.705362 0.02232278 PD1A5 protein disulfide isomerase family A, member 5 1.705199 0.02030493 KIF1C kinesin family member 1C 1.704965 0.0285 1004 UGDH UDP-glucose 6-dehydrogenase 1.704915 0.02264137 RNPEP arginyl aminopeptidase (aminopeptidase B) 1.704725 0.0130882 YEATS2 YEATS domain containing 2 1.704584 0.03356943 SLC43A1 solute carrier family 43, member 1 1.704326 0.01980745 ZNF491 #N/A 1.704156 0.04566768 SUPT3H suppressor of Ty 3 homolog (S. cerevisiae) 1.703882 0.04472675 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CNKSR2 connector enhancer of kinase suppressor of Ras 2 1.703803 0.00125035 TMED8 #N/A 1.703346 0.04469418 ACPI acid phosphatase 1, soluble 1.702812 0.01354428 PNPLA7 patatin-like phospholipase domain containing 7 1.702054 0.01 823767 SPATA5 Spermatogenesis associated 5 1.701947 0.02535752 PPM1J protein phosphatase, Mg2+/Mn2+ dependent, 1J 1.70186 0.00359878 TNFRSF1 #N/A 1.701542 0.01456482 7 ITPR2 inositol 1,4,5-triphosphate receptor, type 2 1.701366 0.04825517 FXYD5 FXYD domain containing ion transport regulator 5 1.701 181 0.0201854 C6orf48 chromosome 6 open reading frame 48 1.70108 0.00120355 PSD4 pleckstrin and Sec7 domain containing 4 1.700869 0.04786245 RGS22 regulator ofG-protein signaling 22 1.700765 0.04004377 TRPC1 transient receptor potential cation channel, 1.700626 0.01678772 subfamily C, member 1 UBE2Q2 ubiquitin-conjugating enzyme E2Q family 1.700414 0.04847906 member 2 SGIP1 SH3-domain GRB2-like (endophilin) interacting 1.69988 0.02289891 protein 1 KBTBD1 1 kelch repeat and BTB (POZ) domain containing 1.699722 0.03785156 11 USP37 ubiquitin specific peptidase 37 1.699715 0.02291508 TMEM79 transmembrane protein 79 1.699667 0.01475681 MCC mutated in colorectal cancers 1.699002 0.01025102 LARGE like-glycosyltransferase 1.698708 0.03318614 ICA1 islet cell autoantigen 1, 69kDa 1.698273 0.02068454 VPS4B vacuolar protein sorting 4 homolog B (S. 1.698022 0.02540869 cerevisiae) LARS2 leucyl-tRNA synthetase 2, mitochondrial 1.697436 0.04425727 CELSR2 cadherin, EGF LAG seven-pass G-type receptor 2 1.69742 0.0062 362 (flamingo homolog, Drosophila) C4orf37 chromosome 4 open reading frame 37 1.697284 0.01673239 PLEKHG pleckstrin homology domain containing, family G 1.696324 0.02681379 7 (with RhoGef domain) member 7 BACH1 BTB and CNC homology 1, basic leucine zipper 1.696301 0.02582705 transcription factor 1 NINL ninein-like 1.696298 0.02549016 SMARCC SWI/SNF related, matrix associated, actin 1.695632 0.03476895 2 dependent regulator of chromatin, subfamily c, member 2 NSUN2 NOP2/Sun domain family, member 2 1.695474 0.04200569 CREB3L4 cAMP responsive element binding protein 3-like 4 1.695449 0.01 57779 UBFD1 ubiquitin family domain containing 1 1.695431 0.03678202 ZNF710 zinc finger protein 710 1.695233 0.03756483 PTGIS #N/A 1.694779 0.04036578 PTDSS1 phosphatidylserine synthase 1 1.694561 0.01229464 TMED4 transmembrane emp24 protein transport domain 1.694517 0.0165239 containing 4 DLG5 discs, large homolog 5 (Drosophila) 1.694485 0.03756438 RU DC2 #N/A 1.693796 0.04140832 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value A LRIG1 leucine-rich repeats and immunoglobulin-like 1.692463 0.01701531 domains 1 RETSAT retinol saturase (all-trans-retinol 13,14-reductase) 1.692359 0.041 1033 PCNT pericentrin 1.692233 0.01662058 ITGAE integrin, alpha E (antigen CD103, human mucosal 1.692199 0.01863436 lymphocyte antigen ; alpha polypeptide) CYLD cylindromatosis (turban tumor syndrome) 1.691563 0.01414714 CCDC1 13 coiled-coil domain containing 113 1.69136 0.03077135 DSTYK dual serine/threonine and tyrosine protein kinase 1.691355 0.00539049 CSMD3 CUB and Sushi multiple domains 3 1.691102 0.02490313 BLVRA biliverdin reductase A 1.690993 0.01560663 DNASE1 deoxyribonuclease I 1.690872 0.04928682 DCTPP1 #N/A 1.690487 0.00930683 FANCD2 Fanconi anemia, complementation group D2 1.69041 0.0401 1305 MAN2B2 mannosidase, alpha, class 2B, member 2 1.690398 0.00707656 POLQ polymerase (DNA directed), theta 1.689642 0.03466341 CYP7B1 #N/A 1.689456 0.0346976 EDARAD EDAR-associated death domain 1.689192 0.00677352 D CPOX coproporphyrinogen oxidase 1.689126 0.04043278 RIFl RAP1 interacting factor homolog (yeast) 1.688849 0.0479608 PRR20 #N/A 1.688646 0.00649377 FHDC1 FH2 domain containing 1 1.688589 0.00499825 GARNL4 GTPase activating Rap/RanGAP domain-like 4 1.688231 0.01702185 SLBP stem-loop binding protein 1.688073 0.00199265 EIF4A2 eukaryotic translation initiation factor 4A2 1.687964 0.03002884 C20orfll2 chromosome 20 open reading frame 112 1.686882 0.01093454 TNP02 transportin 2 1.686825 0.01774808 WDR46 WD repeat domain 46 1.686755 0.00305649 BIN2 bridging integrator 2 1.686613 0.04131404 ADAP2 ArfGAP with dual PH domains 2 1.686238 0.02583013 REG1P regenerating islet-derived 1 pseudogene 1.68621 0.02090773 ZNF302 zinc finger protein 302 1.686208 0.03888947 DOPEY2 dopey family member 2 1.686028 0.02777988 DNAJB12 DnaJ (Hsp40) homolog, subfamily B, member 12 1.685901 0.02182576 TMEM16 transmembrane protein 167B 1.684935 0.03744605 7B B4GALT4 UDP-Gal:betaGlcNAc beta 1,4- 1.684828 0.04699694 galactosyltransferase, polypeptide 4 SEC31A SEC31 homolog A (S. cerevisiae) 1.684689 0.03088132 NR5A2 nuclear receptor subfamily 5, group A, member 2 1.684315 0.02466303 POLG2 polymerase (DNA directed), gamma 2, accessory 1.683536 0.00878715 subunit TUSC5 tumor suppressor candidate 5 1.683376 0.03123336 IDH3A isocitrate dehydrogenase 3 (NAD+) alpha 1.683264 0.04905133 HNRNPL heterogeneous nuclear ribonucleoprotein L 1.683002 0.03736026 AN 3 ankyrin 3, node of Ranvier (ankyrin G) 1.682996 0.00341445 SLC12A4 solute carrier family 12 (potassium/chloride 1.682615 0.00691218 transporters), member 4 DBl/ 69437510.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PVRL1 poliovirus receptor-related 1 (herpesvirus entry 1.682399 0.00467766 mediator C) REPS1 RALBP1 associated Eps domain containing 1 1.682031 0.03344135 LAMA2 laminin, alpha 2 1.6818 0.04749907 BRF1 BRF1 homolog, subunit of RNA polymerase III 1.681429 0.0193653 transcription initiation factor IIIB (S. cerevisiae) KCNC2 potassium voltage-gated channel, Shaw-related 1.681412 0.02312417 subfamily, member 2 PYGM phosphorylase, glycogen, muscle 1.681322 0.03291234 DHX38 DEAH (Asp-Glu-Ala-His) box polypeptide 38 1.681 181 0.04157917 DDIT4L DNA-damage-inducible transcript 4-like 1.680862 0.02337816 BCMOl beta-carotene 15,15'-monooxygenase 1 1.680631 0.00020663 MPRIP myosin phosphatase Rho interacting protein 1.6798 0.01460054 ITGB3 integrin, beta 3 (platelet glycoprotein Ilia, antigen 1.679276 0.00090458 CD61) GRSF1 G-rich RNA sequence binding factor 1 1.67919 0.0373075 LRP5 Low density lipoprotein receptor-related protein 5 1.678925 0.04639084 P4HA3 prolyl 4-hydroxylase, alpha polypeptide III 1.678915 0.0309688 PARP12 poly (ADP-ribose) polymerase family, member 1.678731 0.00841 189 SLC6A3 solute carrier family 6 (neurotransmitter 1.678629 0.04572979 transporter, dopamine), member 3 MYOM3 myomesin family, member 3 1.678119 0.03670593 HIBADH 3-hydroxyisobutyrate dehydro genase 1.67803 0.02993685 LAMB3 laminin, beta 3 1.677836 0.03071771 HMGXB4 HMG box domain containing 4 1.677641 0.02509293 C5orf42 chromosome 5 open reading frame 42 1.67753 0.03526079 KIR2DL4 killer cell immunoglobulin-like receptor, two 1.677121 0.01026487 domains, long cytoplasmic tail, 4 OBSCN obscurin, cytoskeletal calmodulin and titin- 1.676873 0.02544353 interacting RhoGEF LTBP2 latent transforming growth factor beta binding 1.676579 0.03036016 protein 2 MKRN3 makorin ring finger protein 3 1.676295 0.01039506 MGC4580 #N/A 1.676225 0.03605379 0 PDZD2 PDZ domain containing 2 1.676118 0.02083215 DUS2L dihydrouridine synthase 2-like, SMM1 homolog 1.675614 0.03293131 (S. cerevisiae) P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1.675548 0.0278964 1 LBR #N/A 1.675495 0.04944818 BAZ1B bromodomain adjacent to zinc finger domain, IB 1.675443 0.006049 LRRC37A leucine rich repeat containing 37, member A2 1.67535 0.02758695 2 CDK9 #N/A 1.675113 0.04960095 GSTZ1 glutathione transferase zeta 1 1.674763 0.00927053 MAD 1LI MAD1 mitotic arrest deficient-like 1 (yeast) 1.674637 0.02094092 CABIN 1 calcineurin binding protein 1 1.674503 0.00141662 TICAM2 toll-like receptor adaptor molecule 2 1.674473 0.02729191 GOLGA3 golgin A3 1.674292 0.04549478 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value FLNB filamin B, beta 1.674149 0.00227185 PCDH15 Protocadherin 15 1.673851 0.0381 1484 PTPN13 protein tyrosine phosphatase, non-receptor type 13 1.673794 0.0149167 (APO-1/CD95 (Fas)-associated phosphatase) SLC12A5 solute earner family 1 (potassium/chloride 1.673592 0.02038864 transporter), member 5 VPS39 vacuolar protein sorting 39 homolog (S. 1.673251 0.01561087 cerevisiae) OR10G7 Olfactory receptor, family 10, subfamily G, 1.672903 0.00347311 member 7 SLC25A1 solute carrier family 25 (mitochondrial carrier, 1.672861 0.04304577 4 brain), member 14 MGAM maltase-glucoamylase (alpha-glucosidase) 1.672786 0.01935983 TTC17 tetratricopeptide repeat domain 17 1.672722 0.02732361 PTN pleiotrophin 1.672444 0.00274229 SURF2 #N/A 1.671991 0.04659518 IMMT inner membrane protein, mitochondrial 1.671288 0.00538103 MORF4L mortality factor 4 like 2 .670879 0.00982228 2 ARHGAP Rho GTPase activating protein 30 1.670872 0.03033886 30 AADACL #N/A 1.670771 0.00609074 1 ZSWIM3 #N/A 1.67077 0.02358262 BAIAP2L BAI1 -associated protein 2-like 1 1.670402 0.02269513 1 AKAP12 A kinase (PRKA) anchor protein 12 1.670086 0.00481882 KHDRBS KH domain containing, RNA binding, signal 1.670006 0.01783706 2 transduction associated 2 SYNGR2 synaptogyrin 2 1.669943 0.00082102 C7orf70 chromosome 7 open reading frame 70 1.669605 0.0044761 TBCKL #N/A 1.669505 0.01902436 SGCE sarcoglycan, epsilon 1.669432 0.0239744 RAPH1 Ras association (RalGDS/AF-6) and pieckstrin 1.669251 0.01958833 homology domains 1 TRMT5 TRM5 tRNA methyltransferase 5 homolog (S. 1.668629 0.02094255 cerevisiae) IKZF5 #N/A 1.668327 0.01 163852 SDR39U1 #N/A 1.668294 0.02074351 UBL7 ubiquitin-like 7 (bone marrow stromal cell- 1.668008 0.03185661 derived) CD33 CD33 molecule 1.66771 1 0.01845913 DCDC2 doublecortin domain containing 2 1.667659 0.01 155908 ZFAT zinc finger and AT hook domain containing 1.667636 0.03825848 TMC1 transmembrane channel-like 1 1.667431 0.01316726 FER fer (fps/fes related) tyrosine kinase 1.667235 0.0191 1994 TLR4 toll-like receptor 4 1.666932 0.02679148 CCDC22 coiled-coil domain containing 22 1.666931 0.02143564 PPP1R15 #N/A 1.666918 0.00530079 A DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value MYB v-myb myeloblastosis viral oncogene homolog 1.666903 0.03996438 (avian) HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7 1.666809 0.029951 18 SELL selectin L 1.666633 0.02162888 GPR151 #N/A 1.666506 0.00992773 MAP4K2 mitogen-activated protein kinase kinase kinase 1.666455 0.03099083 kinase 2 FGD3 FYVE, RhoGEF and PH domain containing 3 1.666356 0.01460297 PCDHB11 #N/A 1.666195 0.03077624 LYST lysosomal trafficking regulator 1.666014 0.031 10142 OSBPL3 #N/A 1.666006 0.00703659 RHOT2 ras homolog gene family, member T2 1.66596 0.04459323 C12orf4 Chromosome 12 open reading frame 4 1.665847 0.04287477 SPEF1 sperm flagellar 1 1.665351 0.02507237 ETFA electron-transfer-flavoprotein, alpha polypeptide 1.665195 0.02149139 OLIG1 oligodendrocyte transcription factor 1 1.665143 0.00716005 NLRX1 NLR family member X I 1.665095 0.03340494 PDCD2 programmed cell death 2 1.664955 0.02292029 CHN2 chimerin (chimaerin) 2 1.66453 0.0487137 THADA thyroid adenoma associated 1.664419 0.03990602 GLT25D2 glycosyltransferase 25 domain containing 2 1.66425 0.03389155 SCAMP4 #N/A 1.664201 0.02354862 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1.664042 0.02657377 MAOA monoamine oxidase A 1.663427 0.04092647 SYNE1 spectrin repeat containing, nuclear envelope 1 1.663154 0.046808 STAMBP STAM binding protein 1.663149 0.00820563 BRDT bromodomain, testis-specific 1.662949 0.04162642 STAG3L1 stromal antigen 3-like 1 1.662675 0.02648026 ZNF45 zinc finger protein 45 1.662617 0.029321 17 PTCH1 patched homolog 1 (Drosophila) 1.662359 0.01379689 EMB embigin homolog (mouse) 1.661962 0.03133711 ZDHHC4 zinc finger, DHHC-type containing 4 1.66193 0.04152488 AHCYL2 adenosylhomocysteinase-like 2 1.661859 0.02320016 DNAH9 dynein, axonemal, heavy chain 9 1.661616 0.044718 KIF15 kinesin family member 5 1.661378 0.04729327 PPP4R1 protein phosphatase 4, regulatory subunit 1 1.661341 0.02453422 C17orf85 chromosome 17 open reading frame 85 1.660959 0.03169091 SMG7 Smg-7 homolog, nonsense mediated mRNA decay 1.660735 0.03318053 factor (C. elegans) SLC15A4 solute carrier family 15, member 4 1.660637 0.0335626 ROPN1L ropporin 1-like 1.660604 0.04463225 POU2F3 POU class 2 homeobox 3 1.660559 0.00944756 IGF2R insulin-like growth factor 2 receptor 1.66019 0.03101422 BBS4 Bardet-Biedl syndrome 4 1.659758 0.02639537 OR13H1 #N/A 1.659414 0.00175343 PSMD2 proteasome (prosome, macropain) 26S subunit, 1.6591 15 0.01979753 non-ATPase, 2 TCEAL8 #N/A 1.65911 0.0160528 PBRM1 polybromo 1 1.659059 0.00602285 PLEK2 #N/A 1.65905 0.00937674 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upre u ated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ODZ1 odz, odd Oz/ten-m homolog 1(Drosophila) 1.658837 0.03902684 ZYG1 1A zyg-1 1 homolog A (C. elegans) 1.658804 0.03693494 SLC7A7 solute carrier family 7 (cationic amino acid 1.658712 0.02160492 transporter, y+ system), member 7 ZXDC ZXD family zinc finger C 1.65836 0.03600102 FGD6 FYVE, RhoGEF and PH domain containing 6 1.657781 0.0134379 ClorfSO #N/A 1.65773 0.04545184 GPE G protein-coupled estrogen receptor 1 1.657069 0.04319093 USP31 ubiquitin specific peptidase 31 1.656917 0.04971698 SEL1L sel-1 suppressor of lin-12-like (C. elegans) 1.656769 0.00073657 LRRC32 #N/A 1.656648 0.01786459 LOC4011 WD repeat domain 5 pseudogene 1.656331 0.01809748 27 ZFR zinc finger RNA binding protein 1.656317 0.01174294 SFRS1 1 splicing factor, arginine/serine-rich 1 1.655749 0.03570373 DNMT3B #N/A 1.655462 0.0128301 1 LM07 LIM domain 7 1.655296 0.04488696 TMEM87 transmembrane protein 87A 1.654926 0.02492593 A ATL1 atlastin GTPase 1 1.654834 0.04431799 ATP2C2 ATPase, Ca++ transporting, type 2C, member 2 1.654734 0.00487247 SETDB1 SET domain, bifurcated 1 1.654692 0.02047046 EML4 echinoderm microtubule associated protein like 4 1.654476 0.0281831 1 CAD carbamoyl-phosphate synthetase 2, aspartate 1.654177 0.0220691 1 transcarbamylase, and dihydroorotase CADM3 cell adhesion molecule 3 1.65411 0.03872219 IL27RA interleukin 27 receptor, alpha 1.653973 0.01235155 BTBD8 #N/A 1.653912 0.04727336 KLC1 kinesin light chain 1 1.653855 0.02180894 EVI2B ecotropic viral integration site 2B 1.6538 0.0084494 PTCH2 patched homolog 2 (Drosophila) 1.653654 0.04484893 DCTN3 dynactin 3 (p22) 1.653642 0.04236378 ABL2 v-abl Abelson murine leukemia viral oncogene 1.653605 0.02086271 homolog 2 (arg, Abelson-related gene) BMP7 #N/A 1.65329 0.04358522 TP53BP1 tumor protein p53 binding protein 1 1.653193 0.03890936 UBR2 ubiquitin protein ligase E3 component n-recognin 1.653146 0.04514582

SIK2 salt-inducible kinase 2 1.653097 0.03062801 RPS6KA5 ribosomal protein S6 kinase, 90kDa, polypeptide 5 1.652562 0.02190037 GCET2 germinal center expressed transcript 2 1.652415 0.01231915 GRIN3A #N/A 1.652095 0.00100969 PURG #N/A 1.651864 0.01098373 DPT dermatopontin 1.65179 0.00656735 OR6S1 #N/A 1.651297 0.03715299 FXYD6 FXYD domain containing ion transport regulator 6 1.651286 0.01650285 CCR4 #N/A 1.651 135 0.00702746 GJA9 gap junction protein, alpha 9, 59kDa 1.6511 0.00476097 ADNP2 #N/A 1.650976 0.0250456 UBE2F #N/A 1.650727 0.0295403 1/ 694375 6.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ABCB8 ATP-binding cassette, sub-family B (MDR/TAP), 1.650682 0.03026619 member 8 CCT4 chaperonin containing TCP1, subunit 4 (delta) 1.650332 0.00525882 CCNB1 cyclin Bl 1.650164 0.00844464 RAB5B RAB5B, member RAS oncogene family 1.649778 0.01497692 POLH polymerase (DNA directed), eta 1.649547 0.02395011 TTYH3 tweety homolog 3 (Drosophila) 1.649217 0.03137991 RASGEF1 RasGEF domain family, member 1C 1.6491 12 0.00823154 C SETD2 SET domain containing 2 1.648912 0.00785075 RNF216L ring finger protein 216-like 1.648794 0.04043329 FMNL1 formin-like 1 1.648619 0.03552219 CDRT1 CMT1A duplicated region transcript 1 1.6486 0.04368209 ZC3H12A zinc finger CCCH-type containing 12A 1.648404 0.02926977 SARDH #N/A 1.648399 0.03642761 WDR42A WD repeat domain 42A 1.64808 0.04915726 DLGAP1 discs, large (Drosophila) homolog-associated 1.648077 0.0199561 protein 1 SLC10A7 solute carrier family 0 (sodium/bile acid 1.647486 0.02876396 cotransporter family), member 7 HERC3 hect domain and RLD 3 1.647015 0.02552449 ESR2 estrogen receptor 2 (ER beta) 1.646951 0.0465466 TTF2 transcription termination factor, RNA polymerase 1.646301 0.02857324 II SESN2 sestrin 2 1.6461 15 0.02586516 GCNT2 glucosaminyl (N-acetyl) transferase 2, 1-branching 1.645994 0.01314182 enzyme (I blood group) GANC glucosidase, alpha; neutral C 1.645911 0.02361207 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.645215 0.02201527 TOR1AIP torsin A interacting protein 1 1.644946 0.03714375 1 C17orf68 chromosome 17 open reading frame 68 1.644674 0.0394161 ZNF280A #N/A 1.644647 0.02664814 Clorfl63 chromosome 1 open reading frame 163 1.644338 0.03337342 WBSCR2 #N/A 1.643667 0.03986954 2 PLCD1 phospholipase C, delta 1 1.643144 0.0318449 IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 1.642147 0.03956772 NLRP14 NLR family, pyrin domain containing 14 1.642087 0.01706756 GNPAT glyceronephosphate O-acyltransferase 1.64205 0.04891731 ELM02 engulfment and cell motility 2 1.641987 0.0301485 KLHL24 kelch-like 24 (Drosophila) 1.641947 0.04076009 EFNA1 #N/A 1.641752 0.02231982 CSF2RB colony stimulating factor 2 receptor, beta, low- 1.64156 0.04305491 affinity (granulocyte-macrophage) MPST #N/A 1.641559 0.03784384 LYPD1 LY6/PLAUR domain containing 1 1.641321 0.00389105 MFSD6 major facilitator superfamily domain containing 6 1.641239 0.01258127 ZMIZ2 zinc finger, MIZ-type containing 2 1.641094 0.01973167 C6orfl30 chromosome 6 open reading frame 130 1.641034 0.021 16154 DB1/ 6943751 . 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value LRIG3 leucine-rich repeats and immunoglobulin-like 1.640951 0.01573077 domains 3 NDRG2 NDRG family member 2 1.640909 0.03953699 KRTAP9- #N/A 1.640856 0.01242767

ARMC9 armadillo repeat containing 9 1.640715 0.03382256 GK5 glycerol kinase 5 (putative) 1.640432 0.0302701 ABHD12 abhydrolase domain containing 12 1.640414 0.04682013 CD320 #N/A 1.640265 0.02338767 ESR1 estrogen receptor 1 1.639735 0.02625181 SCML2 sex comb on midleg-like 2 (Drosophila) 1.63955 0.02882134 JUP junction plakoglobin 1.639367 0.03601004 CCNE1 cyclin El 1.639327 0.02042491 SPTBN1 spectrin, beta, non-erythrocytic 1 1.63907 0.04864738 SMR3B submaxillary gland androgen regulated protein 3B 1.638949 0.04254077 MAP4 microtubule-associated protein 4 1.638744 0.02496588 ZNF655 zinc finger protein 655 1.638668 0.04149755 E L1 echinoderm microtubule associated protein like 1 1.638472 0.03243667 KLHL18 #N/A 1.638189 0.01732901 VWA5A von Willebrand factor A domain containing 5A 1.638175 0.02082048 FAM71C #N/A 1.638021 0.0465821 GKN1 gastrokine 1 1.637975 0.007651 12 XP05 Exportin 5 1.637723 0.02103416 ZAN zonadhesin 1.637693 0.03842288 C2orf53 chromosome 2 open reading frame 5 1.637664 0.03147439 C l lorf44 chromosome 11 open reading frame 44 1.637585 0.03718475 TDH L-threonine dehydrogenase 1.637032 0.03673551 SLC45A3 solute carrier family 45, member 3 1.63698 0.04169503 UGT1A8 #N/A 1.635808 0.0434691 1 ETNK2 ethanolamine kinase 2 1.635709 0.01409824 Clorfl l 2 chromosome 1 open reading frame 112 1.635579 0.00992461 PGBD1 #N/A 1.635302 0.02192783 TAZ tafazzin 1.63491 0.01976788 SERPINA serpin peptidase inhibitor, clade A (alpha- 1 1.634757 0.0121 1292 J antiproteinase, antitrypsin), member 3 NOTUM #N/A 1.634692 0.03671723 C18orf8 chromosome 18 open reading frame 8 1.634415 0.00563552 CPSF4 cleavage and polyadenylation specific factor 4, 1.634271 0.0401902 30kDa SBDSP Shwachman-Bodian-Diamond syndrome 1.634196 0.00277558 pseudogene ATG7 ATG7 autophagy related 7 homolog (S. cerevisiae) 1.633882 0.03310848 CACNA1 calcium channel, voltage-dependent, R type, alpha 1.633405 0.03050823 E IE subunit TMEM13 #N/A 1.633247 0.04015418 o MTMR6 myotubularin related protein 6 1.6331 11 0.04210798 CCDC96 coiled-coil domain containing 96 1.632721 0.00132894 KLF8 Kruppel-like factor 8 1.632665 0.04518306 CREB3 cAMP responsive element binding protein 3 1.632661 0.0380793 Supplemental Table 2 Gene Transcripts Uprcgulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value IZUMOl izumo sperm-egg fusion 1 1.632556 0.0152677 CCDC151 coiled-coil domain containing 1 1.632357 0.02205364 EXTL3 #N/A 1.632321 0.04837552 ERBB4 v-erb-a erythroblastic leukemia viral oncogene 1.632268 0.01693918 homolog 4 (avian) SETD4 SET domain containing 4 1.632159 0.04029087 MCM7 minichromosome maintenance complex 1.632054 0.02622018 component 7 GPX2 #N/A 1.631438 0.01078967 ZNHIT1 #N/A 1.630944 0.03475841 AMPD2 adenosine monophosphate deaminase 2 1.63062 0.04068794 PvNGTT R A guanylyltransferase and 5'-phosphatase 1.630394 0.03077662 ISY1 ISY1 splicing factor homolog (S. cerevisiae) 1.630243 0.00860759 RFX5 regulatory factor X, 5 (influences HLA class II 1.63004 0.02507788 expression) DUSP14 #N/A 1.629513 0.03743221 PACSIN2 protein kinase C and casein kinase substrate in 1.629416 0.01854641 neurons 2 CDC2L5 Cell division cycle 2-like 5 (cholinesterase-related 1.629232 0.02372003 cell division controller) AGBL4 ATP/GTP binding protein-like 4 1.62914 0.01689332 DCLRE1 DNA cross-link repair IB (PS02 homolog, S. 1.628759 0.04794598 B cerevisiae) KLHL32 kelch-like 3 (Drosophila) 1.628517 0.04424856 BLK B lymphoid tyrosine kinase 1.628505 0.0313156 TRPM7 transient receptor potential cation channel, 1.628499 0.02783676 subfamily M, member 7 RNF170 ring finger protein 170 1.628178 0.03156258 MIER3 mesoderm induction early response 1, family 1.628174 0.01490144 member 3 MX1 myxovirus (influenza virus) resistance 1, 1.628158 0.04340208 interferon-inducible protein p78 (mouse) RABGAP RAB GTPase activating protein 1-like 1.628143 0.04352724 1L METTL2 methyltransferase like 2A 1.627822 0.01062648 A CNOT10 CCR4-NOT transcription complex, subunit 10 1.627757 0.02486744 TCEB2 transcription elongation factor B (SHI), 1.627719 0.03178226 polypeptide 2 (18kDa, elongin B) CUL1 cullin 1 1.627524 0.03912367 HSF2BP heat shock transcription factor 2 binding protein 1.627338 0.0129484 PDIK1L PDLIM1 interacting kinase 1 like 1.627183 0.03847401 DLG4 discs, large homolog 4 (Drosophila) 1.62656 0.03446465 AD adenosine kinase 1.626424 0.0464659 KIF3C kinesin family member 3C 1.626414 0.01997377 KRT86 #N/A 1.625703 0.02397988 ZNF543 zinc finger protein 543 1.625441 0.03427418 GBF1 golgi brefeldin A resistant guanine nucleotide 1.625387 0.02183229 exchange factor 1 ICAM5 intercellular adhesion molecule 5, telencephalin 1.625377 0.04795445 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value HOXB7 homeobox B7 1.625337 0.02032398 SLC39A1 solute carrier family 39 (zinc transporter), member 1.625181 0.02637379 3 13 PNKP polynucleotide kinase 3'-phosphatase 1.624848 0.00781074 SILV silver homolog (mouse) 1.62477 0.00568004 CDH3 cadherin 3, type 1, P-cadherin (placental) 1.624713 0.01 152246 PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 1.6247 0.04549777 (beta) I TS7 integrator complex subunit 7 1.624478 0.04201484 TRIM16 tripartite motif-containing 16 1.624409 0.0204917 RSPH1 #N/A 1.624223 0.00789075 NGLY1 N-glycanase l 1.624181 0.01133855 OR8U1 #N/A 1.623929 0.01915999 PLXNA1 plexin Al 1.623848 0.01642974 TRPT1 TRNA phosphotransferase 1 1.623 538 0.0 1647 146 CLSTN1 calsyntenin 1.623255 0.03128379 ATP2C1 ATPase, Ca++ transporting, type 2C, member 1 1.623069 0.02035012 DHX16 DEAH (Asp-Glu-Ala-His) box polypeptide 16 1.6225 14 0.03058077 ADAM 10 ADAM metallopeptidase domain 10 1.622498 0.02080203 CDC2L6 Cell division cycle 2-like 6 (CDK8-like) 1.622378 0.01975908 FLAD1 FAD1 flavin adenine dinucleotide synthetase 1.622301 0.03 145574 homolog (S. cerevisiae) CDC25A cell division cycle 25 homolog A (S. pombe) 1.621755 0.03357124 KIAA043 KIAA0430 1.621552 0.01950306 0 IFRD2 interferon-related developmental regulator 2 1.621513 0.02552217 GLP1R glucagon-like peptide 1 receptor 1.621275 0.04657262 ACSS2 acyl-CoA synthetase short-chain family member 2 1.621256 0.03220868 AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha 1.621068 0.033041 11 hydroxysteroid dehydrogenase, type II) FOXP1 forkhead bo Pl 1.621009 0.01077085 TRIML1 tripartite motif family-like 1 1.62081 0.04904316 AP3B2 adaptor-related protein complex 3, beta 2 subunit 1.620796 0.0 52866 ACSL4 acyl-CoA synthetase long-chain family member 4 1.620361 0.01663773 UIMC1 ubiquitin interaction motif containing 1 1.619904 0.0123412 GSTK1 glutathione S-transferase kappa 1 1.619571 0.02 1695 4 SLC30A5 solute carrier family 30 (zinc transporter), member 1.619372 0.0061 1784 5 GNRHR gonadotropin-releasing hormone receptor 1.6191 12 0.01836612 MAGI3 membrane associated guanylate kinase, WW and 1.619074 0.0347533 PDZ domain containing 3 KCNS3 #N/A 1.61907 0.0384468 GOLM1 golgi membrane protein 1 1.619055 0.02770539 PPIL2 peptidylprolyl isomerase (cyclophilin)-like 2 1.619019 0.03839263 BBS9 Bardet-Biedl syndrome 9 1.618971 0.02545215 C14orfl66 chromosome 14 open reading frame 166B 1.618766 0.01727413 B FAM13A family with sequence similarity 13, member A 1.618222 0.04696473 ZNF337 zinc finger protein 337 1.618164 0.04917179 SCRN1 secernin l 1.618146 0.0234382 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value RIOK1 RIO kinase 1 (yeast) 1.618073 0.02088876 ZDHHC2 Zinc finger, DHHC-type containing 20 1.617842 0.01970808 nj KCNAB2 potassium voltage-gated channel, shaker-related 1.617684 0.03981078 subfamily, beta member 2 ATP7A ATPase, Cu++ transporting, alpha polypeptide 1.617624 0.0024491 1 ZNF350 zinc finger protein 350 1.617613 0.03540954 AK2 adenylate kinase 2 1.617525 0.02250204 ONECUT #N/A 1.617494 0.0193396

DOCK1 1 dedicator of cytokinesis 11 1.617408 0.01499409 THRSP thyroid hormone responsive (SPOT 14 homolog, 1.617243 0.01840825

Lai J MATN2 matrilin 2 1.6171 11 0.03774538 NOL3 nucleolar protein 3 (apoptosis repressor with 1.616781 0.04753178 CARD domain) CCDC64 coiled-coil domain containing 64 1.616608 0.01778892 TXNDC1 thioredoxin domain containing 12 (endoplasmic 1.616508 0.04404119 2 reticulum) TAF11 TAF1 1 RNA polymerase II, TATA box binding 1.616355 0.04944223 protein (TBP)-associated factor, 28kDa PRKAGl protein kinase, AMP-activated, gamma 1 non- 1.616205 0.01400252 catalytic subunit TNFRSF1 tumor necrosis factor receptor superfamily, 1.6161 16 0.028242 oc member 10c, decoy without an intracellular domain SRD5A3 steroid 5 alpha-reductase 3 1.615868 0.02133345 COR02B coronin, actin binding protein, 2B 1.615597 0.02201055 ARMC2 armadillo repeat containing 2 1.615273 0.04917875 C15orf28 #N/A 1.615065 0.04881938 ADAMI 5 ADAM metallopeptidase domain 15 1.615013 0.04295632 GTF2IRD GTF2I repeat domain containing 2 1.614706 0.0087574

MATR3 matrin 3 1.614624 0.0181 1932 AMDHD1 amidohydrolase domain containing 1 1.613868 0.04706021 NAAA N-acylethanolamine acid amidase 1.613809 0.02682593 ANKRD2 ankyrin repeat domain 26 1.613804 0.02691717

PTCD3 Pentatricopeptide repeat domain 3 1.613309 0.04131451 ACOT4 acyl-CoA thioesterase 4 1.612309 0.01303749 BAT3 HLA-B associated transcript 3 1.612256 0.02485149 SLC1A2 #N/A 1.612239 0.02701275 GSDMC gasdermin C 1.612099 0.03494167 IL2RA #N/A 1.612085 0.001 141 1 MEGF8 multiple EGF-like-domains 8 1.611731 0.04800507 LTK leukocyte receptor tyrosine kinase 1.61 166 0.03101757 SUCLG2 succinate-CoA ligase, GDP-forming, beta subunit 1.61146 0.01434601 WDR3 WD repeat domain 3 1.611359 0.04273902 TNFSF12 tumor necrosis factor (ligand) superfamily, 1.610842 0.03875184 member 12 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ASH2L ash2 (absent, small, or homeotic)-like (Drosophila) 1.610829 0.02280295 CUZD1 CUB and zona pellucida-like domains 1 1.61066 0.036731 16 CDK7 cyclin-dependent kinase 7 1.61064 0.04970104 BSPRY #N/A 1.610422 0.03152908 SLC5A12 solute carrier family 5 (sodium/glucose 1.610288 0.02608645 cotransporter), member 12 DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 1.610267 0.00745079 CPB2 carboxypeptidase B2 (plasma) 1.610111 0.00791 195 CLU clusterin 1.609789 0.01774065 C21orf81 Chromosome 2 open reading frame 8 1.609735 0.02571931 ADRBK1 adrenergic, beta, receptor kinase 1 1.60958 0.04747509 ASCC3 activating signal cointegrator 1 complex subunit 3 1.609556 0.03484109 HPSE heparanase 1.609469 0.02739996 CHD9 chromodomain helicase DNA binding protein 9 1.609356 0.04390294 CYP4B1 cytochrome P450, family 4, subfamily B, 1.60928 0.03068933 polypeptide 1 FBX04 F-box protein 4 1.609254 0.0305442 TRIM72 #N/A 1.609243 0.02288382 TMEM31 #N/A 1.60898 0.00892839 MEGF10 multiple EGF-like-domains 10 1.60862 0.03073571 ZNF567 zinc finger protein 567 1.608258 0.00974876 DDR1 discoidin domain receptor tyrosine kinase 1 1.608256 0.03840132 ZNHIT3 zinc finger, HIT type 3 1.6081 13 0.03646061 UQCC ubiquinol-cytochrome c reductase complex 1.608051 0.04468544 chaperone ZMYM6 zinc finger, MYM-type 6 1.607937 0.03222668 LGALS8 lectin, galactoside-binding, soluble, 8 1.607202 0.03947108 C1QTNF5 Clq and tumor necrosis factor related protein 5 1.607031 0.01353479 DMKN dermokine 1.607017 0.01687905 ITGBL1 integrin, beta-like 1 (with EGF-like repeat 1.606994 0.0452156 domains) C3orf67 #N/A 1.60672 0.03567027 CYP24A1 cytochrome P450, family 24, subfamily A, 1.606438 0.02869597 polypeptide 1 UHRF1BP UHRF1 binding protein 1 1.606348 0.03018077 1 ZFP30 #N/A 1.606079 0.0481 1928 AMY1A amylase, alpha 1A (salivary) 1.606035 0.04665085 BRD9 bromodomain containing 9 1.605968 0.02485162 SBN02 strawberry notch homolog 2 (Drosophila) 1.60563 0.02050891 LAMA3 laminin, alpha 3 1.60535 0.04047009 JUN jun oncogene 1.60477 0.01920584 DEN D2 DENN/MADD domain containing 2D 1.604585 0.0490579 D HP1BP3 heterochromatin protein 1, binding protein 3 1.604565 0.02598613 ITGAM integrin, alpha M (complement component 3 1.604305 0.03035087 receptor 3 subunit) AMMEC AMME chromosomal region gene 1-like 1.604173 0.01373426 R1L Clorf93 chromosome 1 open reading frame 93 1.604147 0.04881347 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fo d Ttest P Symbol Change value PMS2CL #N/A 1.60402 0.01335582 MY018B myosin XVIIIB 1.603928 0.04918494 OR4A16 olfactory receptor, family 4, subfamily A, member 1.60381 0.02967072 16 PDLIM2 PDZ and LIM domain 2 (mystique) 1.603215 0.02290454 SMYD1 #N/A 1.602613 0.03160765 VTA1 Vps20-associated 1 homolog (S. cerevisiae) 1.602593 0.04573813 ACSF2 acyl-CoA synthetase family member 2 1.602582 0.04822356 CEACAM carcinoembryonic antigen-related cell adhesion 1.602541 0.02459421 3 molecule 3 MTM1 #N/A 1.602123 0.03943243 AAAS achalasia, adrenocortical insufficiency, alacrimia 1.601908 0.0452572 (Allgrove, triple-A) GFPT2 glutamine-fructose-6-phosphate transaminase 2 1.601761 0.00786173 NLGN2 neuroligin 2 1.601549 0.02665695 RBP3 retinol binding protein 3, interstitial 1.601508 0.04403107 ATF6 activating transcription factor 6 1.601489 0.0302381 1 MAN1B1 mannosidase, alpha, class IB, member 1 1.60138 0.02061913 CDH5 cadherin 5, type 2 (vascular endothelium) 1.601346 0.04208751 SLC1A4 solute carrier family 1 (glutamate/neutral amino 1.601 111 0.01714116 acid transporter), member 4 TK2 thymidine kinase 2, mitochondrial 1.60101 0.04195181 CITED2 Cbp/p300-interacting transactivator, with 1.600362 0.04147867 Glu/Asp-rich carboxy-terminal domain, 2 FAF2 Fas associated factor family member 2 1.600215 0.00209179 ERP44 endoplasmic reticulum protein 44 1.600078 0.02573524 PLSCR3 #N/A 1.599948 0.00947326 CHTF18 CTF18, chromosome transmission fidelity factor 1.599627 0.04534168 1 homolog (S. cerevisiae) MRC2 mannose receptor, C type 2 1.59955 0.01292167 C16orf82 chromosome 16 open reading frame 82 1.59918 0.02872845 KLB klotho beta 1.599102 0.01424179 DDR2 discoidin domain receptor tyrosine kinase 2 1.598951 0.03041582 AFAP1 actin filament associated protein 1 1.598905 0.04563362 AK3L1 adenylate kinase 3-like 1 1.598791 0.01572813 C8orf33 chromosome 8 open reading frame 33 1.598778 0.03554831 TMEM20 transmembrane protein 206 1.598312 0.00827525 6 TSGA13 Testis specific, 13 1.597388 0.03964771 LRRK1 leucine-rich repeat kinase 1 1.596944 0.01369564 CASP1 caspase 1, apoptosis-related cysteine peptidase 1.596901 0.04141203 (interleukin 1, beta, convertase) PPAN- PPAN-P2RY1 1 readthrough 1.596832 0.02509514 P2RY11 APEH N-acylaminoacyl-peptide hydrolase 1.596762 0.03121484 FBX018 F-box protein, helicase, 8 1.59676 0.02376201 SLITRK3 SLIT and NTRK-like family, member 3 1.596757 0.031 19089 LOC1510 #N/A 1.596188 0.03293784 09 CDC14A CDC14 cell division cycle 14 homolog A (S. 1.595892 0.00154532 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value cerevisiae) RP 1L1 retinitis pigmentosa 1-like 1 1.59584 0.04913338 DACH2 dachshund homolog 2 (Drosophila) 1.595531 0.01838976 TMEM16 #N/A 1.595419 0.00108249

PGGT1B #N/A 1.59504 0.03890081 MTMR 10 myotubularin related protein 10 1.594912 0.01 191 PvDHl 1 retinol dehydrogenase 11 (all-trans/9-cis/l 1-cis) 1.594865 0.03426753 SLC12A6 solute carrier family 12 (potassium/chloride 1.594721 0.01361639 transporters), member 6 PR AAl protein kinase, AMP-activated, alpha 1 catalytic 1.594463 0.04465486 subunit TRRAP transformation/transcription domain-associated 1.593929 0.041873 protein ANK2 ankyrin 2, neuronal 1.593848 0.04658378 TSC1 tuberous sclerosis 1 1.593378 0.0306092 C2CD2 C2 calcium-dependent domain containing 2 1.593314 0.04277642 URM1 #N/A 1.593008 0.0381 188 FBXOll F-box protein 11 1.592841 0.0041492 SH3BP5 SH3-domain binding protein 5 (BTK-associated) 1.592836 0.02379332 B9D1 B9 protein domain 1 1.592734 0.00875643 AFF4 AF4/FMR2 family, member 4 1.592172 0.03735867 GRK7 G protein-coupled receptor kinase 7 1.592054 0.02158491 C9orfl40 chromosome 9 open reading frame 140 1.59201 0.03023132 NF2 neurofibromin 2 (merlin) 1.591993 0.03518012 ATP1 3A3 ATPase type 13A3 1.591824 0.04776691 PIK3R4 phosphoinositide-3-kinase, regulatory subunit 4 1.591757 0.041 18887 UNQ6167 #N/A 1.591575 0.01460981 SMG6 Smg-6 homolog, nonsense mediated mRNA decay 1.591296 0.02366313 factor (C. elegans) TEP1 telomerase-associated protein 1 1.591249 0.007113 ADAMTS ADAMTS-like 1 1.591238 0.0346295 LI JTB jumping translocation breakpoint 1.59121 0.00645786 HEXB hexosaminidase B (beta polypeptide) 1.591 169 0.03643068 CDC42BP CDC42 binding protein kinase gamma (DMPK- 1.591 157 0.03515532 G like) UBR3 ubiquitin protein ligase E3 component n-recognin 1.591072 0.03510366 3 (putative) TTC13 tetratricopeptide repeat domain 13 1.591059 0.01200634 CEP76 centrosomal protein 76kDa 1.59072 0.03796653 CTNND2 catenin (cadherin-associated protein), delta 2 1.590564 0.04139833 (neural plakophilin-related arm-repeat protein) COG2 component of oligomeric golgi complex 2 1.590559 0.03938693 ZNF250 #N/A 1.590509 0.03867041 TWSG1 Twisted gastrulation homolog 1 (Drosophila) 1.590384 0.03366619 BBS 12 Bardet-Biedl syndrome 12 1.590323 0.04737214 ABCC8 ATP-binding cassette, sub-family C (CFTR/MRP), 1.589974 0.02165076 member 8 WNK1 WNK lysine deficient protein kinase 1 1.589806 0.03200462 DBl/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest Symbol Change value C6orfl 14 #N/A 1.58954 0.01063591 LYSMD2 LysM, putative peptidoglycan-binding, domain 1.589339 0.02093268 containing 2 BRSK1 BR serine/threonine kinase 1 1.589014 0.03200387 PCDHGA protocadherin gamma subfamily A, 9 1.58873 0.023841 19 q EAF1 ELL associated factor 1 1.588657 0.02722721 TYW1B tRNA-yW synthesizing protein 1 homolog B (S. 1.588492 0.0202829 cerevisiae) LPCAT2 lysophosphatidylcholine acyltransferase 2 1.588151 0.02446608 SPAG5 sperm associated antigen 5 1.588074 0.0223564 HNF1B HNF1 homeobox B 1.587917 0.0471151 RAB22A RAB22A, member RAS oncogene family 1.587841 0.00540586 CRX cone-rod homeobox 1.587767 0.02490908 TADA2L Transcriptional adaptor 2 (ADA2 homolog, yeast)- 1.587709 0.01967787

v C SMC IB structural maintenance of chromosomes B 1.587648 0.0335672 VPS8 vacuolar protein sorting 8 homolog (S. cerevisiae) 1.587643 0.02836086 HELLS helicase, lymphoid-specific 1.587547 0.04955739 QRICH2 glutamine rich 2 1.587423 0.04650146 EXTL1 exostoses (multiple)-like 1 1.587242 0.0062661 1 KCNK1 potassium channel, subfamily K, member 1 1.587052 0.03835799 CYP27B1 cytochrome P450, family 27, subfamily B, 1.586904 0.00724345 polypeptide 1 RAB2B #N/A 1.586842 0.02741108 ATP6V1C ATPase, H+ transporting, lysosomal 42kDa, V 1 1.586738 0.01862375 2 subunit C2 PHLDB3 #N/A 1.586628 0.04403771 PTPRF protein tyrosine phosphatase, receptor type, F 1.586443 0.00015476 ARMCX5 armadillo repeat containing, X-linked 5 1.586281 0.02579047 KLHL13 kelch-like 13 (Drosophila) 1.585801 0.03290522 LM02 #N/A 1.585683 0.01 178633 MMP19 matrix metallopeptidase 19 1.585515 0.04827345 CCNYL1 cyclin Y-like 1 1.585471 0.02078159 IKBKE inhibitor of kappa light polypeptide gene enhancer 1.585318 0.02560331 in B-cells, kinase epsilon F R Fl receptor 1.585065 0.04318684 GUCY2C guanylate cyclase 2C (heat stable enterotoxin 1.584901 0.0258845 receptor) SAP130 Sin3A-associated protein, 130kDa 1.584898 0.02084365 C1QTNF4 #N/A 1.584857 0.00443819 CSMD2 CUB and Sushi multiple domains 2 1.584718 0.04266615 SDK2 sidekick homolog 2 (chicken) 1.584691 0.00472839 ADAM17 ADAM metallopeptidase domain 17 1.584644 0.02422915 ATR ataxia telangiectasia and Rad3 related 1.584356 0.02047599 IFT88 intraflagellar transport 88 homolog 1.584235 0.03689187 (Chlamydomonas) DNMT3L DNA (cytosine-5-)-methyltransferase 3-like 1.584131 0.02732209 TRIM2 tripartite motif-containing 2 1.583354 0.02097093 NAT 15 N-acetyltransf erase 15 (GCN5-related, putative) 1.583249 0.01793565 D / 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PPBP pro-platelet basic protein (chemokine (C-X-C 1.583184 0.04417932 motif) ligand 7) SORCS1 sortilin-related VPS 10 domain containing receptor 1.583089 0.00145216 1 PTPRK protein tyrosine phosphatase, receptor type, K 1.582954 0.03883168 ERCC6 excision repair cross-complementing rodent repair 1.582855 0.03693582 deficiency, complementation group 6 C19orf45 chromosome 19 open reading frame 45 1.582827 0.01372364 NARG1L NMDA receptor regulated 1-like 1.582732 0.01 141 116 PPAP2A phosphatidic acid phosphatase type 2A 1.582666 0.00144035 DYSF dysferlin, limb girdle muscular dystrophy 2B 1.582554 0.02005849 (autosomal recessive) ADAM23 ADAM metallopeptidase domain 23 1.582461 0.03598515 CDH8 cadherin 8, type 2 1.582411 0.01416816 COG3 component of oligomeric golgi complex 3 1.58219 0.03076747 PDE4D phosphodiesterase 4D, cAMP-specific 1.582152 0.03999691 (phosphodiesterase E3 dunce homolog, Drosophila) POT1 protection of telomeres 1 homolog (S. pombe) 1.582129 0.00425704 ATP1A1 ATPase, Na+/K+ transporting, alpha 1 polypeptide 1.582011 0.01059971 GRIK4 #N/A 1.581954 0.03740164 ZNF397 zinc finger protein 397 1.581557 0.0359701 CCDC50 coiled-coil domain containing 50 1.581327 0.02701904 FLJ13197 hypothetical FLJ13 197 1.580835 0.02393229 EMD #N/A 1.580701 0.0428735 RASA3 RAS p21 protein activator 3 1.580655 0.03063955 FAM40B family with sequence similarity 40, member B 1.580347 0.014431 12 MME membrane metallo-endopeptidase 1.580337 0.00628201 AARSD1 alanyl-tRNA synthetase domain containing 1 1.580146 0.0094374 RDH12 retinol dehydrogenase 12 (all-trans/9-cis/l 1-cis) 1.579889 0.03674629 HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.579603 0.03605033 SDCBP syndecan binding protein (syntenin) 1.579519 0.0221665 C10orfl40 chromosome 10 open reading frame 140 1.579379 0.02057772 CAPN11 calpain 1 1.579255 6.95E-05 KANK1 K motif and ankyrin repeat domains 1 1.578484 0.0289754 ASPH aspartate beta-hydroxylase 1.57833 0.03437934 TSR1 TSR1, 20S rRNA accumulation, homolog (S. 1.578152 0.01061894 cerevisiae) TRABD TraB domain containing 1.578042 0.00509686 EPHB4 EPH receptor B4 1.577896 0.04990407 ATP6V1A ATPase, H+ transporting, lysosomal 70kDa, VI 1.57784 0.02526282 subunit A CELSR1 cadherin, EGF LAG seven-pass G-type receptor 1 1.577518 0.04498579 (flamingo homolog, Drosophila) MFSD9 major facilitator superfamily domain containing 9 1.577044 0.00544493 ZDHHC2 zinc finger, DHHC-type containing 2 1.576589 0.00927643 DSC3 desmocollin 3 1.576479 0.02893414 CROCCL ciliary rootlet coiled-coil, rootletin-like 1 1.576179 0.02536792 1 TNFRSF6 #N/A 1.575991 0.03266746 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value B ATP2B2 ATPase, Ca++ transporting, plasma membrane 2 1.575985 0.038121 12 APOB apolipoprotein B (including Ag(x) antigen) 1.575935 0.01844524 ID2 inhibitor of DNA binding 2, dominant negative 1.575791 0.03728961 helix-loop-helix protein TMEM44 #N/A 1.575589 0.04537621 CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.575574 0.04508288 D2 subunit 2 LSAMP #N/A 1.575408 0.01726092 AFG3L1 AFG3 ATPase family gene 3-like 1 (S. cerevisiae) 1.575401 0.0228751 1 C17orf63 chromosome open reading frame 63 1.575341 0.04826082 BACE2 beta-site APP-cleaving enzyme 2 1.575246 0.02393872 FAM160A family with sequence similarity 160, member A2 1.575216 0.04868855

ER 1 endoplasmic reticulum to nucleus signaling 1 1.575111 0.01643217 GNPTG N-acetylglucosamine- 1-phosphate transferase, 1.575093 0.03895541 gamma subunit GAGE1 G antigen 1 1.574721 0.01644645 SCAMPI secretory carrier membrane protein 1 1.57467 0.02157253 MAP3K10 mitogen-activated protein kinase kinase kinase 0 1.5746 0.01164556 GBE1 glucan (1,4-alpha-), branching enzyme 1 1.57458 0.04179094 CP ceruloplasmin (ferroxidase) 1.574574 0.03721093 E2F5 E2F transcription factor 5, pl30-binding 1.574504 0.0411 1575 POU5F1 POU class 5 homeobox 1 1.574427 0.03206344 GDF7 Growth differentiation factor 7 1.574369 0.01239241 USP12 ubiquitin specific peptidase 12 1.574275 0.0169693 SLC13A4 solute carrier family 13 (sodium/sulfate 1.573872 0.02546365 symporters), member 4 SNHG7 #N/A 1.573774 0.0131859 BAGE B melanoma antigen 1.573499 0.00573789 IQWD1 IQ motif and WD repeats 1 1.573388 0.00690926 POLE2 polymerase (DNA directed), epsilon 2 (p59 1.573351 0.0499254 subunit) CDKL1 cyclin-dependent kinase-like 1 (CDC2 -related 1.573026 0.03198318 kinase) SNAPC3 small nuclear R A activating complex, 1.572895 0.04873285 polypeptide 3, 50kDa ALMS1 Alstrom syndrome 1 1.57257 0.03754191 USP20 ubiquitin specific peptidase 20 1.572495 0.00964908 OLA1 Obg-like ATPase 1 1.57241 0.02014899 SLC35B4 solute carrier family 35, member B4 1.572356 0.03579128 TRAF5 TNF receptor-associated factor 5 1.572202 0.0118116 SIM2 single-minded homolog 2 (Drosophila) 1.57188 0.0363994 KLK7 kallikrein-related peptidase 7 1.571556 0.00602879 FAM107B family with sequence similarity 107, member B 1.571462 0.0499209 MYL10 #N/A 1.571408 0.019907 UMODL1 uromodulin-like 1 1.571 159 0.03245662 CTN A1 catenin (cadherin-associated protein), alpha 1, 1.57067 0.03967257 102kDa ZNF540 #N/A 1.5705 0.04629319 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value VPS35 Vacuolar protein sorting 35 homolog (S. 1.570291 0.04981512 cerevisiae) SLC37A1 solute carrier family 37 (glycerol-3-phosphate 1.570203 0.0479174 transporter), member 1 LOCI 001 similar to zinc finger protein 799 1.570005 0.03452717 34396 SLC7A1 1 solute carrier family 7, (cationic amino acid 1.569962 0.03388442 transporter, y+ system) member 1 EZH2 enhancer of zeste homolog 2 (Drosophila) 1.569822 0.03248874 TMEM22 #N/A 1.569714 0.04624286 2 PRPH peripherin 1.569551 0.03010769 DUSP13 dual specificity phosphatase 3 1.569365 0.00698188 IER5 Immediate early response 5 1.569239 0.03059287 JMJD8 jumonji domain containing 8 1.569201 0.00186703 EZH1 enhancer of zeste homolog 1 (Drosophila) 1.569122 0.03681327 ADCK2 aarF domain containing kinase 2 1.568919 0.00764036 MAN2B1 mannosidase, alpha, class 2B, member 1 1.568772 0.00431642 ITIH1 inter-alpha (globulin) inhibitor H 1.568705 0.04038838 PRKAG3 protein kinase, AMP-activated, gamma 3 non- 1.568554 0.01 129936 catalytic subunit C6orf64 chromosome 6 open reading frame 64 1.568482 0.0473454 KRBA1 KRAB-A domain containing 1 1.568336 0.0353163 PREX2 phosphatidylinositol-3,4,5-trisphosphate- 1.568106 0.03016754 dependent Rac exchange factor 2 PARP14 poly (ADP-ribose) polymerase family, member 4 1.567929 0.04751239 GATSL3 GATS protein-like 3 1.567334 0.01 14682 UBE2CBP ubiquitin-conjugating enzyme E2C binding protein 1.5672 0.04470765 FAM124B #N/A 1.567171 0.01266934 NAT1 N-acetyltransferase 11 1.567117 0.0194771 NCOA6 nuclear receptor coactivator 6 1.567033 0.01622988 VPS26B vacuolar protein sorting 26 homolog B (S. pombe) 1.566785 0.04307642 VDAC3 voltage-dependent anion channel 3 1.566756 0.04059678 GPAM Glycerol-3 -phosphate acyltransferase, 1.566595 0.01625274 mitochondrial PARP4 poly (ADP-ribose) polymerase family, member 4 1.566571 0.04244339 TMC03 transmembrane and coiled-coil domains 3 1.566566 0.03901138 PPP2R5D protein phosphatase 2, regulatory subunit B', delta 1.566442 0.01 11716 UBE3C ubiquitin protein ligase E3C 1.566387 0.00552304 OR4D6 #N/A 1.566317 0.04814622 SMPDL3 sphingomyelin phosphodiesterase, acid-like 3A 1.566308 0.03912803 A C18orf45 chromosome 8 open reading frame 45 1.566288 0.00811821 Z F438 zinc finger protein 438 1.566126 0.00965156 RHBDF1 #N/A 1.565929 0.02802746 CDH15 cadherin 15, type 1, M-cadherin (myotubule) 1.565886 0.04710114 PCDH1 1X protocadherin 11 X-linked 1.565808 0.03880194 RTTN rotatin 1.565788 0.04473924 PEX3 peroxisomal biogenesis factor 3 1.565712 0.01551155 IQCBl IQ motif containing Bl 1.565602 0.01077869 DB 1/ 69437516.1! Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value TRPM2 transient receptor potential cation channel, 1.565244 0.02674605 subfamily M, member 2 STAT2 signal transducer and activator of transcription 2, 1.565101 0.00586589 13kDa FLJ44048 FLJ44048 protein 1.564904 0.03758947 AFF3 AF4/FMR2 family, member 3 1.564708 0.0283746 O 3A4 #N/A 1.564682 0.041 17352 DVL3 dishevelled, dsh homolog 3 (Drosophila) 1.564642 0.02434656 DNAH11 dynein, axonemal, heavy chain 11 1.564592 0.0414389 NT5C 5', 3'-nucleotidase, cytosolic 1.56457 0.0446903 SPEN spen homolog, transcriptional regulator 1.564499 0.0233066 (Drosophila) TMPRSS1 transmembrane protease, serine 13 1.564484 0.0368793 3 C20orfl49 Chromosome 20 open reading frame 149 1.564392 0.00222356 DGKH Diacylglycerol kinase, eta 1.564346 0.0367789 FYCOl FYVE and coiled-coil domain containing 1 1.564045 0.02623964 IL23R interleukin 23 receptor 1.563714 0.00338447 APBA1 amyloid beta (A4) precursor protein-binding, 1.563618 0.02990328 family A, member 1 CACNA1 calcium channel, voltage-dependent, T type, alpha 1.563523 0.01013023 G 1G subunit SLC9A3R #N/A 1.563271 0.04801348 1 UBE4B ubiquitination factor E4B (UFD2 homolog, yeast) 1.563098 0.04789056 ST13 suppression of tumorigenicity 13 (colon 1.563085 0.02759531 carcinoma) (Hsp70 interacting protein) THOC3 THO complex 3 1.562977 0.01573792 VTI1A vesicle transport through interaction with t- 1.562647 0.02759378 SNAREs homolog 1A (yeast) CD 6 cyclin-dependent kinase 6 1.56261 0.02902345 YPEL2 #N/A 1.562551 0.04389314 ATRIP ATR interacting protein 1.562549 0.03935309 FAM170A family with sequence similarity 170, member A 1.562187 0.01403262 AGGF1 angiogenic factor with G patch and FHA domains 1.561939 0.01752432 1 LRP8 Low density lipoprotein receptor-related protein 8, 1.561638 0.01283334 apolipoprotein e receptor CLEC17A C-type lectin domain family 17, member A 1.561512 0.03881722 TEC Tec protein tyrosine kinase 1.561419 0.04835099 UBE2J1 ubiquitin-conjugating enzyme E2, Jl (UBC6 1.561325 0.03932752 homolog, yeast) LTBR lymphotoxin beta receptor (TNFR superfamily, 1.56131 0.01734089 member 3) DBR1 debranching enzyme homolog 1 (S. cerevisiae) 1.560804 0.04423254 ADAM 19 ADAM metallopeptidase domain 19 (meltrin beta) 1.56073 0.01586926 EFHD1 EF-hand domain family, member Dl 1.560486 0.04485476 SGOL2 shugoshin-like 2 (S. pombe) 1.560043 0.03657261 TPP2 tripeptidyl peptidase II 1.559247 0.02199587 UCP2 #N/A 1.558711 0.02231615 DBl/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value FCAMR #N/A 1.558696 0.02610126 SPATA21 spermatogenesis associated 2 1 1.55863 0.04292467 SP100 SP100 nuclear antigen 1.558535 0.04252481 BAIAP2 BAI1 -associated protein 2 1.55851 1 0.02805553 COPZ1 Coatomer protein complex, subunit zeta 1 1.55847 0.02752252 ARFGEF1 ADP-ribosylation factor guanine nucleotide- 1.558221 0.00719994 exchange factor l(brefeldin A-inhibited) HNF1A F1NF1 homeobox A 1.558103 0.02276896 AAG 1 kidney associated antigen 1 1.557843 0.01686161 HUNK hormonally up-regulated Neu-associated kinase 1.557667 0.02915042 HK2 hexokinase 2 1.557123 0.01528673 ECHDC2 enoyl CoA hydratase domain containing 2 1.55701 0.03188733 FGFRIOP FGFR1 oncogene partner 1.556994 0.04220555 SLC20A2 solute carrier family 20 (phosphate transporter), 1.556953 0.02206856 member 2 FLU flightless I homolog (Drosophila) 1.556875 0.03932867 TMEM17 #N/A 1.556793 0.04308751 4 CELSR3 cadherin, EGF LAG seven-pass G-type receptor 3 1.556787 0.03262012 (flamingo homolog, Drosophila) PSME4 proteasome (prosome, macropain) activator 1.556614 0.00839984 subunit 4 WDR26 WD repeat domain 26 1.556435 0.04076079 FL Friend leukemia virus integration 1 1.556366 0.04141388 SPAG1 A sperm associated antigen 11A 1.55631 0.04413696 DIAPH2 diaphanous homolog 2 (Drosophila) 1.556277 0.02283721 PHF7 #N/A 1.556238 0.02309381 GDF1 growth differentiation factor 1 1.556024 0.01715961 PNPLA6 patatin-like phospholipase domain containing 6 1.555804 0.03083244 ITGA5 integrin, alpha 5 (fibronectin receptor, alpha 1.555713 0.03160453 polypeptide) ZAK sterile alpha motif and leucine zipper containing 1.555553 0.04046045 kinase AZK ZPBP zona pellucida binding protein 1.555489 0.03469015 OR1L6 #N/A 1.555362 0.04907249 BIRC7 baculoviral IAP repeat-containing 7 1.555356 0.00560653 PALB2 partner and localizer of BRCA2 1.554951 0.03269141 GOLPH3 golgi phosphoprotein 3-like 1.554927 0.02287013 L COL1 1A2 collagen, type XI, alpha 2 1.554906 0.01062953 BTBD9 #N/A 1.554815 0.00414556 IQGAP3 IQ motif containing GTPase activating protein 3 1.554802 0.03180541 ZNF516 zinc finger protein 516 1.554729 0.03327762 INTU inturned planar cell polarity effector homolog 1.554677 0.01093947 (Drosophila) VAT1L vesicle amine transport protein 1 homolog (T. 1.554477 0.02672044 californica)-like GAS 8 growth arrest-specific 8 1.55427 0.0138367 PTBP2 polypyrimidine tract binding protein 2 1.553715 0.02025571 MERTK c-mer proto-oncogene tyrosine kinase 1.553644 0.00740715 DBl/69437516. Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value USP24 ubiquitin specific peptidase 24 1.553516 0.04241653 ZNF703 zinc finger protein 703 1.553516 0.0157481 TMEM12 transmembrane protein 1 0A 1.553488 0.03978529 OA KDM4A lysine (K)-specific demethylase 4A 1.55346 0.00643308 NMI N-myc (and STAT) interactor 1.553368 0.03407941 SLC5A1 solute carrier family 5 (sodium/glucose 1.553159 0.04013204 cotransporter), member 1 FLJ20184 #N/A 1.55307 0.03693891 CCDC55 coiled-coil domain containing 55 1.552793 0.04222151 CCDC45 coiled-coil domain containing 45 1.552779 0.0417771 1 JAG2 jagged 2 1.552759 0.01734602 GFM1 G elongation factor, mitochondrial 1 1.55256 0.00540147 FCHSD2 FCH and double SH3 domains 2 1.552543 0.03357263 ACY3 aspartoacylase (aminocyclase) 3 1.552438 0.0317794 PSRC1 proline/serine-rich coiled-coil 1 1.552427 0.01596017 SMYD2 SET and MYND domain containing 2 1.552349 0.04941773 FAM164C #N/A 1.552223 0.013121 1 STYXL1 #N/A 1.551782 0.04061065 OSBP2 oxysterol binding protein 2 1.551576 0.00327305 KIAA031 KIAA0317 1.55151 0.0065551 7 ASNS asparagine synthetase (glutamine-hydrolyzing) 1.551478 0.04490557 IER3IP1 immediate early response 3 interacting protein 1 1.551439 0.03462929 IGF1R insulin-like growth factor 1 receptor 1.551408 0.0245575 RBM19 RNA binding motif protein 1 1.551308 0.04234767 TLN2 talin 2 1.550999 0.03609548 SERPINA serpin peptidase inhibitor, clade A (alpha- 1 1.55087 0.0466949 10 antiproteinase, antitrypsin), member 0 ACSL6 acyl-CoA synthetase long-chain family member 6 1.550367 0.02772304 STK32A serine/threonine kinase 32A 1.549828 0.0158544 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene 1.549809 0.03913273 homolog 2, neuro/glioblastoma derived oncogene homolog (avian) ACER2 alkaline ceramidase 2 1.5498 0.00666805 YIPF3 Yi l domain family, member 3 1.549456 0.04816962 COX17 COX 17 cytochrome c oxidase assembly homolog 1.548985 0.00063577 (S. cerevisiae) PSMD12 proteasome (prosome, macropain) 26S subunit, 1.54839 0.03297181 non-ATPase, 12 SELENBP selenium binding protein 1 1.548317 0.01943454 1 PSMG1 proteasome (prosome, macropain) assembly 1.548169 0.04325353 chaperone 1 GLB1L3 galactosidase, beta 1-like 3 1.548144 0.041 16442 DDX51 DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 1 1.548135 0.04765583 PRKACG #N/A 1.548002 0.01972037 GSK3A glycogen synthase kinase 3 alpha 1.547597 0.01055153 ELOVL2 elongation of very long chain fatty acids 1.547361 0.02213573 (FENl/Elo2, SUR4/Elo3, yeast)-like 2 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value DYNC1I1 dynein, cytoplasmic 1, intermediate chain 1 1.547255 0.0015712 CD207 CD207 molecule, langerin 1.5472 0.03436793 PIK3C2B phosphoinositide-3-kinase, class 2, beta 1.5472 0.02408928 polypeptide TTC39A tetratricopeptide repeat domain 39A 1.547186 0.0477246 KIFC2 kinesin family member C2 1.547163 0.0048121 1 KIAA119 KIAA1 199 1.547159 0.02909628 9 LIX1L Lixl homolog (mouse)-like 1.547006 0.03097144 LILRA1 leukocyte immunoglobulin-like receptor, 1.546952 0.02348155 subfamily A (with TM domain), member 1 MLLT10 myeloid/lymphoid or mixed-lineage leukemia 1.546189 0.01475505 (trithorax homolog, Drosophila); translocated to, 10 AP1GBP1 API gamma subunit binding protein 1 1.545631 0.04628375 OFD1 Oral-facial-digital syndrome 1 1.54549 0.02426386 FAM98A family with sequence similarity 98, member A .545402 0.02057287 LXN latexin 1.545208 0.04708531 TRA@ T cell receptor alpha locus 1.545 191 0.00657499 ZNF189 zinc finger protein 189 1.545129 0.04371332 PTPN18 protein tyrosine phosphatase, non-receptor type 18 1.5449 0.04522658 (brain-derived) UGCGL1 UDP-glucose ceramide glucosyltransferase-like 1 1.544741 0.01624691 KCNA3 potassium voltage-gated channel, shaker-related 1.544534 0.02801233 subfamily, member 3 C7orf67 #N/A 1.544427 0.03800144 MYLIP myosin regulatory light chain interacting protein 1.544082 0.02225968 C20orfl52 #N/A 1.543931 0.01685434 C6orf81 chromosome 6 open reading frame 8 1 1.54353 1 0.00896843 SLC25A3 solute carrier family 25, member 37 1.543338 0.04649296 7 TTC27 tetratricopeptide repeat domain 27 1.543211 0.03112533 PDE6G phosphodiesterase 6G, cGMP-specific, rod, 1.543173 0.01344947 gamma IFT140 intraflagellar transport 140 homolog 1.543108 0.00515536 (Chlamydomonas) C3orf20 chromosome 3 open reading frame 20 1.543101 0.04849387 ZBTB47 zinc finger and BTB domain containing 47 1.542984 0.00160036 RENBP renin binding protein 1.542802 0.01242357 TRIM29 tripartite motif-containing 29 1.54276 0.01564357 SEMA3F sema domain, immunoglobulin domain (Ig), short 1.542713 0.00446777 basic domain, secreted, (semaphorin) 3F TES testis derived transcript (3 LIM domains) 1.542686 0.0424636 HACE1 HECT domain and ankyrin repeat containing, E3 1.542661 0.02637332 ubiquitin protein ligase 1 SPAM1 sperm adhesion molecule 1 (PH-20 hyaluronidase, 1.542344 0.01501086 zona pellucida binding) LAT2 linker for activation of T cells family, member 2 1.542234 0.02423761 PDIA6 protein disulfide isomerase family A, member 6 1.541958 0.00282884 HGD homogentisate 1,2-dioxygenase 1.541734 0.03666332 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ZWI T ZW10 interactor 1.541193 0.00639813 SLC47A1 solute carrier family 47, member 1 1.540958 0.0236242 USP2 ubiquitin specific peptidase 2 1.540856 0.04579272 ADCY5 adenylate cyclase 5 1.540403 0.04203521 CCDC13 coiled-coil domain containing 13 1.540379 0.03994005 RNF112 #N/A 1.539982 0.03805617 WDR13 WD repeat domain 13 1.53985 0.02618777 AMICA1 Adhesion molecule, interacts with CXADR 1.539542 0.01280107 antigen 1 SLC4A10 solute carrier family 4, sodium bicarbonate 1.53954 0.03531248 transporter, member 10 DSC2 desmocollin 2 1.539479 0.04756335 HERV- #N/A 1.539437 0.04566891 FRD ZNF643 zinc finger protein 643 1.53922 0.02783205 PARP16 poly (ADP-ribose) polymerase family, member 16 1.538958 0.04677215 HOXD13 homeobox D13 1.538795 0.00363393 DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 1.538718 0.04766504 11 (CHLl-like helicase homolog, S. cerevisiae) HOXA11 homeobox All 1.538588 0.01564044 MDH1 malate dehydrogenase 1, NAD (soluble) 1.538547 0.0350328 FARSA #N/A 1.538532 0.04749653 OLIG2 #N/A 1.538087 0.01262021 PBX2 pre-B-cell leukemia homeobox 2 1.537608 0.01562364 PCDHGB #N/A 1.53751 0.04615183 3 TMEM17 transmembrane protein 73 1.537442 0.03398467 3 KL 13 #N/A 1.537286 0.00357254 HIP1 huntingtin interacting protein 1 1.537285 0.04332192 AOX1 aldehyde oxidase 1 1.537229 0.04739972 C20orf96 #N/A 1.537172 0.0308458 GRIN2C glutamate receptor, ionotropic, N-methyl D- 1.536935 0.02623653 aspartate 2C STXBP5 syntaxin binding protein 5 (tomosyn) 1.536748 0.00536101 CYFIP2 cytoplasmic FMR1 interacting protein 2 1.536689 0.04088386 MED28 mediator complex subunit 28 1.53664 0.01080206 GRIA4 glutamate receptor, ionotrophic, AMPA 4 1.536595 0.01793461 HEATR4 HEAT repeat containing 4 1.536414 0.01645114 FANCA Fanconi anemia, complementation group A 1.536412 0.00551397 FAHD2A fumarylacetoacetate hydrolase domain containing 1.536351 0.00138557 2A TBC1D13 #N/A 1.536327 0.04038732 ROR2 receptor tyrosine kinase-like orphan receptor 2 1.536322 0.04734429 ABCA1 ATP-binding cassette, sub-family A (ABC1), 1.53626 0.0201419 member 1 CEBPB CCAAT/enhancer binding protein (C/EBP), beta 1.536196 0.00556252 Clorf52 chromosome 1 open reading frame 52 1.536076 0.00413615 MORC3 MORC family CW-type zinc finger 3 1.535949 0.0052928 CDC42SE CDC42 small effector 1 1.535703 0.04839242 DBl/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 1 PIK3C2G phosphoinositide-3 -kinase, class 2, gamma 1.535554 0.03320153 polypeptide PHF16 PHD finger protein 16 1.535433 0.01452813 KIAA121 KIAA1217 1.535428 0.03370106 7 POLA2 polymerase (DNA directed), alpha 2 (70kD 1.535227 0.01959815 subunit) RBM42 #N/A 1.534781 0.0450143 TFE3 transcription factor binding to IGHM enhancer 3 1.534772 0.01746548 TMEM22 transmembrane protein 220 1.534598 0.01084762 0 Clorfl09 chromosome 1 open reading frame 109 1.534453 0.02284748 BCAT2 branched chain amino-acid transaminase 2, 1.534292 0.04597044 mitochondrial U Q6493 #N/A 1.53402 0.01826442 TBKBP1 TBK1 binding protein 1 1.533859 0.01832024 PPP1R12 #N/A 1.533806 0.01552649 B FANCM #N/A 1.533762 0.04244972 NID2 nidogen 2 (osteonidogen) 1.533745 0.04354743 AVIL advillin 1.533621 0.029517 C4orf23 chromosome 4 open reading frame 23 1.533607 0.04939469 CHPvD chordin 1.533076 0.00878228 SCN9A sodium channel, voltage-gated, type IX, alpha 1.532799 0.00567101 subunit BACH2 BTB and CNC homology , basic leucine zipper 1.53273 0.00813943 transcription factor 2 DISP1 dispatched homolog 1 (Drosophila) 1.532601 0.04747084 CACNA1 calcium channel, voltage-dependent, L type, alpha 1.532479 0.03917101 S I S subunit NHEDC1 Na+/H+ exchanger domain containing 1 1.532385 0.04775145 EXOC3 exocyst complex component 3 1.53236 0.03192753 PH G2 phosphorylase kinase, gamma 2 (testis) 1.532241 0.03755378 LAPTM4 lysosomal protein transmembrane 4 beta 1.531927 0.01663365 B SRPK2 SFRS protein kinase 2 1.531659 0.03108475 ClorflOl chromosome 1 open reading frame 101 1.531 197 0.03580263 MGC3340 #N/A 1.531067 0.03094266 7 CDH26 cadherin 26 1.530946 0.02848122 ATP6V0E ATPase, H+ transporting, lysosomal 9kDa, V0 1.530942 0.02829998 1 subunit el CPNE3 copine III 1.530783 0.01178837 OCIAD2 #N/A 1.530762 0.03368961 ANKMY2 ankyrin repeat and MYND domain containing 2 1.530745 0.03959362 DGKZ diacylglycerol kinase, zeta 104kDa 1.530732 0.01213983 COX18 #N/A 1.530722 0.03748606 TRIM28 tripartite motif-containing 28 1.530532 0.03840176 ST7 suppression of tumorigenicity 7 1.530312 0.02388241 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CNPY4 canopy 4 homolog (zebrafish) 1.530129 0.04723845 LSS lanosterol synthase (2,3-oxidosqualene-lanosterol 1.529869 0.02730441 cyclase) MST02P misato homolog 2 pseudogene 1.529674 0.02938553 HRH2 #N/A 1.529572 0.02613059 DYNC1I2 dynein, cytoplasmic 1, intermediate chain 2 1.529406 0.03549435 PBX1 pre-B-cell leukemia homeobox 1 1.529339 0.00602163 WWOX WW domain containing oxidoreductase 1.529309 0.04842444 GTSE1 G-2 and S-phase expressed 1 1.529293 0.04317673 PRELID2 PPvELI domain containing 2 1.529074 0.04146019 PDLIM7 PDZ and L M domain 7 (enigma) 1.528889 0.02434886 DONSON downstream neighbor of SON 1.528846 0.0376529 SNAPC4 small nuclear RNA activating complex, 1.528841 0.0292172 polypeptide 4, 190kDa RASGRF2 Ras protein-specific guanine nucleotide-releasing 1.528519 0.02536069 factor 2 TBCCD 1 TBCC domain containing 1 1.528518 0.04802688 NMNAT1 nicotinamide nucleotide adenylyltransf erase 1 1.528446 0.02435834 GAGE2A #N/A 1.528331 0.00046436 XYLT1 xylosyltransf erase I 1.52831 0.02859266 ARL 5 ADP-ribosylation factor-like 15 1.528169 0.04972766 SLAMF6 SLAM family member 6 1.527986 0.03142929 B D3 bromodomain and WD repeat domain containing 3 1.527275 0.00310356 FLJ32065 Hypothetical protein FLJ32065 1.527232 0.03715658 EDEM1 ER degradation enhancer, mannosidase alpha-like 1.527109 0.009607 1 EFCAB4B #N/A 1.527087 0.03311729 MBOAT2 membrane bound O-acyltransferase domain 1.526811 0.04662587 containing 2 TP53TG3 #N/A 1.526577 0.01798109 RPGR retinitis pigmentosa GTPase regulator 1.526564 0.03311823 IVNS 1AB influenza virus NS1A binding protein 1.526505 0.04656562 P C3orfl Chromosome 3 open reading frame 1 1.526467 0.02580067 TCERGIL transcription elongation regulator 1-like 1.526411 0.03687745 RTEL1 regulator of telomere elongation helicase 1 1.526194 0.02923067 PIAS4 protein inhibitor of activated STAT, 4 1.526122 0.04829212 RRAGC Ras-related GTP binding C 1.525906 0.01474772 CIITA class II, major histocompatibility complex, 1.525854 0.04492051 transactivator SCN2A sodium channel, voltage-gated, type II, alpha 1.5257 0.00243559 subunit GALNT5 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.525654 0.04313718 N-acetylgalactosaminyltransferase 5 (GalNAc-T5) PCIF1 PDX1 C-terminal inhibiting factor 1 1.525599 0.01919144 SSX3 #N/A 1.525589 0.01438453 C 9orf6 chromosome open reading frame 6 1.525428 0.02554083 SMEK1 SMEK homolog 1, suppressor of mekl 1.525278 0.02973042 (Dictyostelium) AKAP4 #N/A 1.525002 0.02279171 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PELI2 pellino homolog 2 (Drosophila) 1.524603 0.00735412 HEATR1 HEAT repeat containing 1 .524537 0.02752963 ARR3 arrestin 3, retinal (X-arrestin) 1.524478 0.0043137 UNC5C unc-5 homolog C (C. elegans) 1.524469 0.04499824 UGT2B15 #N/A 1.52436 0.02623177 SOX4 SRY (sex determining region Y)-box 4 1.524227 0.00886675 TTLL3 tubulin tyrosine ligase-like family, member 3 1.524 11 0.00736764 FLT3LG fms-related tyrosine kinase 3 ligand 1.524077 0.01 175394 SSH1 slingshot homolog 1 (Drosophila) 1.523977 0.04184018 VIM vimentin 1.523884 0.04124592 PODXL podocalyxin-like 1.523804 0.00861833 ZNF436 zinc finger protein 436 1.523707 0.04067693 ZNF433 zinc finger protein 433 1.523594 0.01444774 PPARGC1 peroxisome proliferator-activated receptor gamma, 1.523461 0.01858888 B coactivator 1 beta COL9A1 collagen, type IX, alpha 1 1.523327 8.24E-05 PLCE1 phospholipase C, epsilon 1 1.523254 0.01 15958 DNAJC4 DnaJ (Hsp40) homolog, subfamily C, member 4 .523 92 0.031 86698 ZNF286A zinc finger protein 286A 1.522884 0.03164334 ANKRD2 ankyrin repeat domain 28 1.522866 0.0295649 8 C7orf42 chromosome 7 open reading frame 42 1.522728 0.04504565 TAF2 TAF2 RNA polymerase II, TATA box binding 1.522666 0.045 12762 protein (TBP)-associated factor, 150kDa TSC22D2 TSC22 domain family, member 2 1.522282 0.0030166 C4A complement component 4A (Rodgers blood group) 1.522279 0.043 17567 RYR1 ryanodine receptor 1 (skeletal) 1.522278 0.0461507 RBPMS2 RNA binding protein with multiple splicing 2 1.522198 0.01969139 TGIF1 TGFB-induced factor homeobox 1 .522064 0.01450587 AHSA2 AHA1, activator of heat shock 90kDa protein 1.522001 0.04031996 ATPase homolog 2 (yeast) SCN3A sodium channel, voltage-gated, type III, alpha .5 1 23 0.02607254 subunit LIMD1 LIM domains containing 1 1.52191 1 0.04640935 ZMYND1 #N/A 1.521834 0.02496381 2 ITGA10 integrin, alpha 10 1.521524 0.00959363 HEXA hexosaminidase A (alpha polypeptide) .52 144 0.03564508 ST8SIA4 ST8 alpha-N-acetyl-neuraminide alpha-2,8- 1.52 1432 0.01 744928 sialyltransferase 4 CAV1 caveolin l . caveolae protein, 22kDa 1.521415 0.03791804 ALDH7A aldehyde dehydrogenase 7 family, member A l 1.52121 1 0.04933379 1 BEST3 bestrophin 3 1.521204 0.0388346 CACNB2 calcium channel, voltage-dependent, beta 2 1.521042 0.00676234 subunit TGM1 #N/A 1.521018 0.03581708 ARMC6 armadillo repeat containing 6 1.520888 0.02893813 ADAPI ArfGAP with dual PH domains 1 1.520758 0.0364661 KCNK10 #N/A 1.520752 0.04920474 DBi; 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CLASP2 #N/A 1.520681 0.04356009 TN I3 troponin I type 3 (cardiac) 1.520515 0.03944469 EIF4ENIF eukaryotic translation initiation factor 4E nuclear 1.520404 0.00348984 1 import factor 1 ZNF615 zinc finger protein 615 1.520245 0.02108454 FLT3 fms-related tyrosine kinase 3 1.520185 0.01322775 A2ML1 #N/A 1.519952 0.00890104 CR1 complement component (3b/4b) receptor 1 (Knops 1.519948 0.0278393 blood group) EVC2 Ellis van Creveld syndrome 2 1.519929 0.02167464 IGHM #N/A 1.519861 0.04848814 DEPDC4 DEP domain containing 4 1.519762 0.03247166 HVCN1 hydrogen voltage-gated channel 1 1.51976 0.02238518 HSPB1 heat shock 27kDa protein 1 1.519678 0.02359025 RGS6 regulator of G-protein signaling 6 1.519587 0.04840437 AKD2 #N/A 1.519497 0.01294726 RIN3 Ras and Rab interactor 3 1.519438 0.03060739 IMPG2 Interphotoreceptor matrix proteoglycan 2 1.518982 0.01469147 SEPSECS Sep (O-phosphoserine) tRNA:Sec (selenocysteme) 1.518354 0.02087681 tRNA synthase RGS7 regulator of G-protein signaling 7 1.518207 0.01586147 ZNF778 zinc finger protein 778 1.518154 0.01480456 OPRM1 opioid receptor, u 1 1.518105 0.00314228 DOCK 10 dedicator of cytokinesis 10 1.518044 0.02778568 KIN KIN, antigenic determinant of recA protein 1.517916 0.03923584 homolog (mouse) ZNF507 zinc finger protein 507 1.51731 0.00611545 TBC1D3 TBC1 domain family, member 3 1.517061 0.03974991 APOC2 #N/A 1.516825 0.03157728 GRAMD1 GRAM domain containing 1C 1.516205 0.04967244 C PROCR protein C receptor, endothelial 1.516129 0.01491359 C3AR1 complement component 3a receptor 1 1.515918 0.01581 163 PDE4DIP phosphodiesterase 4D interacting protein 1.515754 0.01390453 CLEC1 1A #N/A 1.515747 0.0440781 KIAA171 KIAA1712 1.515593 0.04527365 2 PRY PTPN13-like, Y-linked 1.515345 0.01405544 PTGFR #N/A 1.515272 0.01227869 MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 1.515093 0.01956442 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 1.51498 0.0095039 SLC25A1 solute carrier family 25 (mitochondrial carrier; 1.514693 0.04630693 0 dicarboxylate transporter), member 10 MCOLN2 mucolipin 2 1.51452 0.04997968 Clorfl98 chromosome 1 open reading frame 8 1.514489 0.00459002 FAM176A family with sequence similarity 176, member A 1.514341 0.04276084 CBS #N/A 1.5142 0.04132355 MYST4 MYST histone acetyltransferase (monocytic 1.51419 0.04610093 leukemia) 4 EML5 echinoderm microtubule associated protein like 5 1.514188 0.01607303 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SPG7 spastic paraplegia 7 (pure and complicated 1.51408 0.0262147 autosomal recessive) METTL7 #N/A 1.514022 0.01042424 B COL1 1A1 collagen, type XI, alpha 1 1.514014 0.00257131 PPFIBP2 #N/A 1.513922 0.01840277 TRPA1 transient receptor potential cation channel, 1.513861 0.01788238 subfamily A, member 1 OR5P3 #N/A 1.513725 0.02916868 NEK1 NIMA (never in mitosis gene a)-related kinase 1 1.513498 0.00670321 ABCA13 ATP-binding cassette, sub-family A (ABC1), 1.513479 0.02456736 member 13 ZNF3970 #N/A 1.513279 0.00197526 S TAF4 TAF4 RNA polymerase II, TATA box binding 1.513223 0.03373199 protein (TBP)-associated factor, 135kDa AGPAT6 #N/A 1.512954 0.03524408 SLC25A4 solute carrier family 25, member 45 1.512932 0.01025411 5 TDRD7 tudor domain containing 7 1.512892 0.03268637 C8orf46 chromosome 8 open reading frame 46 1.512723 0.03182585 PHF20 PHD finger protein 20 1.512697 0.02352271 PEF1 #N/A 1.51265 0.00099369 KLK2 kallikrein-related peptidase 2 1.512505 0.01798366 CYP2C8 #N/A 1.512442 0.03768932 RAPGEF2 Rap guanine nucleotide exchange factor (GEF) 2 1.512434 0.02678822 MRVI1 murine retrovirus integration site 1 homolog 1.5121 19 0.02275801 KCNMA1 potassium large conductance calcium-activated 1.512118 0.02490189 channel, subfamily M, alpha member 1 RFC4 replication factor C (activator 1) 4, 37kDa 1.51195 0.00433235 TES 2 #N/A 1.51 1917 0.03606908 TIAM2 T-cell lymphoma invasion and metastasis 2 1.511809 0.00026137 LAMA5 laminin, alpha 5 1.51 1632 0.02817024 ERAP1 #N/A 1.511626 0.02847767 CHN1 chimerin (chimaerin) 1 1.51 1498 0.03848462 TEX261 testis expressed 261 1.51 1333 0.04895197 EFNB2 ephrin-B2 1.51 1313 0.0281 1974 HSF2 heat shock transcription factor 2 1.511271 0.02081911 BLOC1S2 biogenesis of lysosomal organelles complex- , 1.51 1216 0.02923129 subunit 2 C1QL2 complement component 1, q subcomponent-like 2 1.51 1 1 13 0.0491 1363 THUMPD THUMP domain containing 3 1.510729 0.03991285 3 NUMA1 nuclear mitotic apparatus protein 1 1.510652 0.02466567 MAP4K1 mitogen-activated protein kinase kinase kinase 1.510576 0.01999283 kinase 1 GRAMD3 GRAM domain containing 3 1.510198 0.03505043 PET1 12L #N/A 1.509642 0.03583531 GSTTP1 glutathione S-transferase theta pseudogene 1 1.509243 0.01952154 ZNF18 zinc finger protein 18 1.509015 0.01040435 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value TNNI1 troponin I type 1 (skeletal, slow) 1.508775 0.0212851 1 NSAP1 1 nervous system abundant protein 11 1.508701 0.02008257 LARP6 #N/A 1.50845 0.0051241 DDB2 damage-specific DNA binding protein 2, 48kDa 1.50842 0.04650229 PGM3 phosphoglucomutase 3 1.508225 0.01688132 CCDC135 coiled-coil domain containing 135 1.50795 0.02160831 CARD 11 caspase recruitment domain family, member 11 1.507431 0.03283898 ACOT13 acyl-CoA thioesterase 13 1.507239 0.04251 16 LPHN3 latrophilin 3 1.50705 0.01904418 IQCE IQ motif containing E 1.506926 0.03294537 NLRP6 N/A 1.506865 0.00737172 WWC2 WW and C2 domain containing 2 1.506714 0.02348157 EIF4EBP3 #N/A 1.506626 0.00694641 hCG_2431 #N/A 1.506625 0.00885811 2 ZBTB11 zinc finger and BTB domain containing 11 1.506409 0.02793328 SFRS15 splicing factor, arginine/serine-rich 15 1.506266 0.01961 157 ZNF354B zinc finger protein 354B 1.50625 0.02066909 RASGRP3 RAS guanyl releasing protein 3 (calcium and 1.506213 0.00673812 DAG-regulated) RIC8A resistance to inhibitors of cholinesterase 8 1.506025 0.04323676 homolog A (C. elegans) CD226 #N/A 1.505998 0.04475406 PPM1L protein phosphatase, Mg2+/Mn2+ dependent, 1L 1.505912 0.04544897 LNPEP leucyl/cystinyl aminopeptidase 1.505637 0.04502002 CLASP 1 cytoplasmic linker associated protein 1 1.505522 0.02046148 SMPD2 sphingomyelin phosphodiesterase 2, neutral 1.505414 0.04020793 membrane (neutral sphingomyelinase) CREB3L3 #N/A 1.505349 0.03244781 MEMOl Mediator of cell motility 1 1.505264 0.0182921 NCR3 natural cytotoxicity triggering receptor 3 1.505256 0.00048627 DE D1 DENN/MADD domain containing 1C 1.505248 0.03090044 C C5orf24 chromosome 5 open reading frame 24 1.505156 0.04864502 ELM03 engulfment and cell motility 3 1.505156 0.01966598 LRRC37A leucine rich repeat containing 37, member A4 1.504995 0.04713156 4 (pseudogene) TMEM8 Transmembrane protein 8 (five membrane- 1.504856 0.01099229 spanning domains) GABRD gamma-aminobutyric acid (GABA) A receptor, 1.504786 0.00463672 delta CPA3 carboxypeptidase A3 (mast cell) 1.504658 0.04232725 BAT4 HLA-B associated transcript 4 1.504622 0.04859982 TKT transketolase 1.504378 0.04523652 APOM apolipoprotein M 1.503803 0.0393742 BIRC3 #N/A 1.503709 0.00258758 USP40 ubiquitin specific peptidase 40 1.503395 0.00413796 CD86 #N/A 1.503289 0.03540023 IL27 #N/A 1.503053 0.04791632 C9orfl71 #N/A 1.502746 0.03462208 DBl/ 09437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value RSBN1 round spermatid basic protein 1 1.502467 0.01937463 COBL cordon-bleu homolog (mouse) 1.502347 0.02524997 ITGAL integrin, alpha L (antigen CD1 1A ( i 80), 1.502314 0.00920043 lymphocyte function-associated antigen 1; alpha polypeptide) PLS1 plastin 1 1.502107 0.03009453 DAAM2 dishevelled associated activator of morphogenesis 1.501909 0.02196621 2 ZNF595 zinc finger protein 595 1.501845 0.03326776 LAMB2 laminin, beta 2 (laminin S) 1.501796 0.0297375 LUZP6 leucine zipper protein 6 1.501732 0.03627483 ODF2L outer dense fiber of sperm tails 2-like 1.501589 0.02970323 TEKT1 tektin 1 1.501499 0.0160542 ZSCAN5 zinc finger and SCAN domain containing 5A 1.501432 0.01523309 A DNAI1 dynein, axonemal, intermediate chain 1 1.501239 0.02589567 WDR72 WD repeat domain 72 1.501077 0.03810376 PRKD3 protein kinase D3 1.500973 0.04375189 GGT7 gamma-glutamyltransferase 7 1.500897 0.0300489 PRSS1 #N/A 1.500792 0.00210628 EPC1 enhancer of polycomb homolog 1 (Drosophila) 1.500699 0.03620974 LK1 kallikrein-related peptidase 12 1.500604 0.04722164 OR5K1 #N/A 1.500599 0.01846902 PCDHGA #N/A 1.500514 0.01932019 2 CREM cAMP responsive element modulator 1.500393 0.01481585 GPR177 G protein-coupled receptor 177 1.500203 0.04882108 IL16 interleukin 6 (lymphocyte chemoattractant factor) 1.499957 3.09E-06 ATP13A4 ATPase type 13A4 1.499852 0.02048198 RNF125 #N/A 1.499719 0.02868188 WDR78 WD repeat domain 78 1.499613 0.03715928 TSHZ2 #N/A 1.499495 0.03449735 MUM1L1 melanoma associated antigen (mutated) 1-like 1 1.499362 0.02683646 Clorf97 #N/A 1.499283 0.00436052 LOXL2 lysyl oxidase-like 2 1.499279 0.00303413 C1GALT1 core 1 synthase, glycoprotein-N- 1.499215 0.03790968 acetylgalactosamine 3-beta-galactosyltransferase, 1 SLC44A1 solute carrier family 44, member 1 1.499123 0.00699643 DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X- 1.498945 0.00547769 linked HAUS6 HAUS augmin-like complex, subunit 6 1.498882 0.02557891 ClOorflO #N/A 1.498872 0.01613471 TBC1D3B #N/A 1.498802 0.01035539 CCDC93 coiled-coil domain containing 93 1.498678 0.02519198 ACOX3 acyl-CoA oxidase 3, pristanoyl 1.498653 0.01323784 HSPBAP1 HSPB (heat shock 27kDa) associated protein 1 1.498525 0.03297875 SLC30A6 solute carrier family 30 (zinc transporter), member 1.498497 0.03691582 6 TEX13B testis expressed 13B 1.498463 0.04611241 DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upreguiated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PAMR1 peptidase domain containing associated with 1.498358 0.03428594 muscle regeneration 1 ARHGEF Rho guanine nucleotide exchange factor (GEF) 17 1.498327 0.02393166 17 ZBP1 Z-DNA binding protein 1 1.498245 0.01453906 ABCA1 1P ATP-binding cassette, sub-family A (ABC1), 1.498181 0.04124259 member 11 (pseudogene) ENAH enabled homolog (Drosophila) 1.498006 0.01643479 C10orf99 #N/A 1.497989 0.04485341 DNAJC10 DnaJ (Hsp40) homolog, subfamily C, member 10 1.497865 0.03664069 MAP3K9 mitogen-activated protein kinase kinase kinase 9 1.497852 0.04433363 MYLK3 myosin light chain kinase 3 1.497596 0.03993566 EXOl exonuclease 1 1.497513 0.01883602 UBQLN2 ubiquilin 2 1.497031 0.04532667 KATNB1 katanin p80 (WD repeat containing) subunit B 1 1.496953 0.02780858 ADAM11 ADAM metallopeptidase domain 11 1.496387 0.00656196 KANK2 KN motif and ankyrin repeat domains 2 1.496305 0.04455511 BID BH3 interacting domain death agonist 1.496027 0.04501775 SMAD1 SMAD family member 1 1.495787 0.01473042 ADAMTS ADAMTS-like 5 1.495476 0.03975532 L5 TBC1D20 #N/A 1.495357 0.03391408 PIGR #N/A 1.495263 0.037885 MAP3K3 mitogen-activated protein kinase kinase kinase 3 1.495253 0.01286347 PDZK1P1 PDZ domain containing 1 pseudogene 1 1.495225 0.04915917 HEATR6 HEAT repeat containing 6 1.495068 0.00184054 ZNF136 zinc finger protein 136 1.494622 0.03399777 DAAM1 dishevelled associated activator of morphogenesis 1.494444 0.00094922 1 TNFRSF9 tumor necrosis factor receptor superfamily, 1.494407 0.04184248 member 9 GPX6 Glutathione peroxidase 6 (olfactory) 1.494389 0.00809537 NSUN5 NOP2/Sun domain family, member 5 1.494193 0.017034 ING3 inhibitor of growth family, member 3 1.493899 0.0089448 ABCA9 ATP-binding cassette, sub-family A (ABC1), 1.493891 0.04695243 member 9 WR Werner syndrome, RecQ helicase-like 1.493874 0.04009878 PLXNB1 plexin Bl 1.493586 0.04305745 RIT1 Ras-like without CAAX 1 1.493381 0.00705308 C9orfl25 chromosome 9 open reading frame 125 1.493371 0.02103353 DCBLD1 discoidin, CUB and LCCL domain containing 1 1.492919 0.0084101 1 EIF3B eukaryotic translation initiation factor 3, subunit B 1.492839 0.00826051 HSPG2 heparan sulfate proteoglycan 2 1.492714 0.02841941 POLR2B polymerase (RNA) II (DNA directed) polypeptide 1.492545 0.0174615 B, 140kDa UNC93B1 unc-93 homolog B1 (C. elegans) 1.492491 0.0071786 SPACA1 #N/A 1.492342 0.01694002 ADAT2 adenosine deaminase, tRNA-specific 2, TAD2 1.492002 0.00662497 homolog (S. cerevisiae) ST7L suppression of tumorigenicity 7 like 1.491995 0.03027795 DB1/ 6943751 6.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SLC30A4 solute carrier family 0 (zinc transporter), member 1.491871 0.02964738 4 CEP 170 centrosomal protein 170kDa 1.491814 0.03664036 C6orfll8 Chromosome 6 open reading frame 118 1.491666 0.02077073 DNASE1 deoxyribonuclease I-like 2 1.491477 0.02179018 L2 GCA grancalcin, EF-hand calcium binding protein 1.491456 0.04370834 CYP2R1 Cytochrome P450, family 2, subfamily R, 1.491451 0.02409106 polypeptide 1 CNTLN centlein, centrosomal protein 1.491392 0.011 17339 SRMS src-related kinase lacking C-terminal regulatory 1.491372 0.01927997 tyrosine and N-terminal myristylation sites HOOK3 hook homolog 3 (Drosophila) 1.491337 0.01026371 NPHP3 nephronophthisis 3 (adolescent) 1.491291 0.01239694 MTA1 metastasis associated 1 1.49122 0.03802427 ELAVL3 ELAV (embryonic lethal, abnormal vision, 1.491 151 0.0469912 Drosophila)-like 3 (Hu antigen C) RAD52 RAD 52 homolog (S. cerevisiae) 1.491061 0.03958894 SEC31B SEC31 homolog B (S. cerevisiae) 1.490681 0.01933014 UGT3A1 UDP glycosyltransferase 3 family, polypeptide A l 1.490658 0.03668628 Clorfl23 chromosome 1 open reading frame 123 1.490522 0.04120738 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 1.490522 0.04072548 KIR2DS2 #N/A 1.490465 0.00909117 PRDM10 PR domain containing 1.490369 0.03714741 TUBA4A tubulin, alpha 4a 1.489974 0.01531328 TRIM 15 tripartite motif-containing 5 1.489745 0.02704514 DEN D1 DENN/MADD domain containing IB 1.489693 0.03803935 B PDE11A phosphodiesterase 11A 1.489508 0.01033018 HIVEP2 human immunodeficiency virus type I enhancer 1.489475 0.01296614 binding protein 2 CPSF1 cleavage and polyadenylation specific factor 1, 1.489363 0.0145321 1 160kDa GCOM1 GRTNLIA complex locus 1.489269 0.03293698 SLC18A2 solute carrier family 18 (vesicular monoamine), 1.489234 0.01707352 member 2 SNAP91 #N/A 1.489193 0.00852122 B3GNT8 #N/A 1.488864 0.01925139 VPRBP Vpr (HIV-1) binding protein 1.48869 0.04377584 PSD3 pleckstrin and Sec7 domain containing 3 1.488596 0.01387586 SP2 Sp2 transcription factor 1.488555 0.00776772 MKS1 Meckel syndrome, type 1 1.488428 0.04044232 MAGEA2 melanoma antigen family A, 2 1.487961 0.02809906 CSRPl cysteine and glycine-rich protein 1 1.487678 0.01 194748 METTL3 methyltransferase like 3 1.487554 0.03923316 FLJ25006 #N/A 1.487515 0.03409879 DOCK4 dedicator of cytokinesis 4 1.487201 0.04840538 TCHH trichohyalin 1.487154 0.03428957 MRPL37 mitochondrial ribosomal protein L37 1.487072 0.02957386 ITSN1 intersectin 1 (SH3 domain protein) 1.487022 0.0462667 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SNX9 sorting nexin 9 1.486758 0.01594801 EIF2C3 eukaryotic translation initiation factor 2C, 3 1.486683 0.0 173 166 TCN2 transcobalamin II 1.486551 0.02764432 GALK2 galactokinase 2 1.486521 0.02855803 TTC8 #N/A 1.486322 0.00425549 PADI3 peptidyl arginine deiminase, type III 1.486121 0.03493482 MFAP3 microfibrillar-associated protein 3 1.486056 0.01292446 NAALAD #N/A 1.486029 0.03891559 L I PGCP plasma glutamate carboxypeptidase 1.485871 0.00774448 CXXC1 CXXC finger 1 (PHD domain) 1.485842 0.02022819 IFNGR1 interferon gamma receptor 1 1.485695 0.03541863 ADRA1A adrenergic, alpha- 1A-, receptor 1.485596 0.03294264 NBEAL2 neurobeachin-like 2 1.485448 0.03417637 ZNF285A #N/A 1.485359 0.04852051 MTHFS 5,10-methenyltetrahydrofolate synthetase (5- 1.485152 0.03172732 formyltetrahydrofolate cyclo-ligase) INTS12 integrator complex subunit 12 1.485117 0.04854864 TSGA10 testis specific, 10 1.485017 0.01942415 AGXT2L1 #N/A 1.484978 0.04359196 VAMP5 #N/A 1.48482 0.02867714 XPR1 xenotropic and polytropic retrovirus receptor 1 1.484626 0.045761 8 FLJ43879 FLJ43879 protein 1.484599 0.01941404 LDHB lactate dehydrogenase B 1.484571 0.01769543 OTOF otoferlin 1.484425 0.00548029 WDR8 WD repeat domain 8 1.484219 0.0073097 CCBL2 cysteine conjugate-beta lyase 2 1.484133 0.04898507 GLIPR2 #N/A 1.483972 0.00476043 FOXK2 forkhead box 2 1.483924 0.0323877 CCDC25 coiled-coil domain containing 25 1.483805 0.01005576 MTTP microsomal triglyceride transfer protein 1.48369 0.023871 16 PLEKHA pleckstrin homology domain containing, family A 1.483463 0.021 8927 7 member 7 MDM1 Mdm4, transformed 3T3 cell double minute l , p53 1.483439 0.02488512 binding protein (mouse) CYP51A1 cytochrome P450, family , subfamily A, 1.483035 0.00605888 polypeptide 1 C12orf37 chromosome 12 open reading frame 37 1.483014 0.0199483 FTCD formiminotransferase cyclodeaminase 1.482859 0.03637955 C8orf68 #N/A 1.482849 0.02731009 NFATC2I nuclear factor of activated T-cells, cytoplasmic, 1.482615 0.03403372 P calcineurin-dependent 2 interacting protein BMPER BMP binding endothelial regulator 1.48251 0.01666766 UGT2B17 UDP glucuronosyltransferase 2 family, 1.482313 0.04353663 polypeptide B17 XRN2 5'-3' exoribonuclease 2 1.482291 0.03334524 6-Mar #N/A 1.482159 0.00620696 ZNF777 zinc finger protein 777 1.481987 0.01421451 SAP30BP SAP30 binding protein 1.481963 0.02114436 CACNA1 calcium channel, voltage-dependent, P/Q type, 1.480764 0.0107704 DB1/ 694 3 75 16.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value A alpha 1A subunit POLR3B polymerase (RNA) III (DNA directed) polypeptide 1.480662 0.0463736 B UBE2D4 #N/A 1.480249 0.01448582 GRM5 glutamate receptor, metabotropic 5 1.480165 0.02136922 MTFR1 mitochondrial fission regulator 1 1.480156 0.01636382 CLDND2 claudin domain containing 2 1.480138 0.03516792 OTUB1 #N/A 1.479936 0.01364523 RBBP6 retinoblastoma binding protein 6 1.479665 0.04940251 MED20 mediator complex subunit 20 1.479368 0.0142524 ANKRD4 ankyrin repeat domain 44 1.478832 0.02380591 4 CREB3L2 cAMP responsive element binding protein 3-like 2 1.478797 0.02076942 ADCY6 adenylate cyclase 6 1.478713 0.01974027 DCI dodecenoyl-CoA isomerase 1.478667 0.03647473 FLJ23834 Hypothetical protein FLJ23834 1.478424 0.04820602 ZKSCAN zinc finger with KRAB and SCAN domains 5 1.478392 0.03120821 5 FBX08 F-box protein 8 1.478277 0.03152013 LAMC2 laminin, gamma 2 1.478091 0.04729644 ANKRD5 #N/A 1.477698 0.00101494 4 MINK1 misshapen-like kinase 1 (zebrafish) 1.47757 0.01754182 NXN nucleoredoxin 1.477182 0.02929918 FASTKD3 FAST kinase domains 3 1.477163 0.0107589 SH3GLB2 SH3-domain GRB2-like endophilin B2 1.477091 0.03236397 CCDC81 coiled-coil domain containing 81 1.477054 0.01975538 PELI1 pellino homolog 1 (Drosophila) 1.47698 0.03398163 DOCK2 dedicator of cytokinesis 2 1.476523 0.02244916 WISP1 #N/A 1.47606 0.01719529 BGLAP #N/A 1.476055 0.00738682 KLHDC6 Kelch domain containing 6 1.476055 0.03928562 ATM ataxia telangiectasia mutated 1.476006 0.04252303 PTPRT protein tyrosine phosphatase, receptor type, T 1.475416 0.02958476 OR2T1 1 Olfactory receptor, family 2, subfamily T, member 1.475392 0.00841785 11 FANCL Fanconi anemia, complementation group L 1.475368 0.03468102 GRB14 growth factor receptor-bound protein 14 1.475083 0.03764759 TCF15 transcription factor 15 (basic helix-loop-helix) 1.474894 0.00719009 TGFBR2 #N/A 1.474842 0.03290676 C2orf28 chromosome 2 open reading frame 28 1.474813 0.01733917 CUBN cubilin (intrinsic factor-cobalamin receptor) 1.474557 0.04055775 COQ2 coenzyme Q2 homolog, prenyltransferase (yeast) 1.474367 0.02612499 LTBP4 latent transforming growth factor beta binding 1.474245 0.00585024 protein 4 LIG1 ligase I, DNA, ATP-dependent 1.474139 0.00096638 ACAP2 ArfGAP with coiled-coil, ankyrin repeat and PH 1.474102 0.04857355 domains 2 ABCG1 ATP-binding cassette, sub-family G (WHITE), 1.473995 0.03561249 member 1 DB1/ 6943 7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value USH1G #N/A 1.473589 0.04293844 CXXC4 #N/A 1.473497 0.04456624 MAT2A methionine adenosyltransferase II, alpha 1.473436 0.00549543 Clorf96 chromosome 1 open reading frame 96 1.473276 0.00325284 SLC4A3 solute carrier family 4, anion exchanger, member 3 1.472698 0.01015349 VWCE von Willebrand factor C and EGF domains 1.472335 0.02063716 MAPK10 mitogen-activated protein kinase 10 1.472218 0.04166794 FAM151B family with sequence similarity 151, member B 1.471846 0.03385216 NEB nebulin 1.471836 0.0064173 SAG S-antigen; retina and pineal gland (arrestin) 1.471714 0.02154346 ABCG5 ATP-binding cassette, sub-family G (WHITE), 1.471531 0.03879777 member 5 CDK3 cyclin-dependent kinase 3 1.471323 0.0023621 1 TNS4 tensin 4 1.47103 0.04334127 HBP1 HMG-box transcription factor 1 1.470971 0.0181465 IL20 interleukin 20 1.470955 0.03946544 ZNF335 zinc finger protein 335 1.470915 0.01884214 SNX31 sorting nexin 31 1.470781 0.04653324 CCDC19 coiled-coil domain containing 1 1.470698 0.01932886 DZIP3 DAZ interacting protein 3, zinc finger 1.470608 0.04900261 ASXL1 additional sex combs like 1 (Drosophila) 1.470256 0.00998521 CYTH2 cytohesin 2 1.470054 0.01718416 FAM12A #N/A 1.469785 0.01492526 KCNG3 potassium voltage-gated channel, subfamily G, 1.46964 0.0456643 member 3 M PS9 mitochondrial ribosomal protein S9 1.469423 0.03660104 FLNC filamin C, gamma 1.469361 0.04022687 SORL1 sortilin-related receptor, L(DLR class) A repeats- 1.469308 0.03912596 containing C15orf44 chromosome 15 open reading frame 44 1.469079 0.00230053 ZCCHC9 zinc finger, CCHC domain containing 9 1.46906 0.04658745 USP33 ubiquitin specific peptidase 33 1.468906 0.04743185 GP2 glycoprotein 2 (zymogen granule membrane) 1.468867 0.04707864 MFN1 mitofusin 1 1.468406 0.0499737 RCOR2 REST corepressor 2 1.46834 0.04187092 ZCCHC4 #N/A 1.467774 0.039209 CAPRIN2 caprin family member 2 1.46771 1 0.0334225 NELF nasal embryonic LHRH factor 1.467618 0.04955878 Clorf51 chromosome 1 open reading frame 51 1.467414 0.0324553 RNF216 ring finger protein 2 1 1.467405 0.03527836 C19orf28 chromosome 19 open reading frame 28 1.467382 0.00690267 TBCE tubulin folding cofactor E 1.467239 0.02970097 SH3GL3 SH3-domain GRB2-like 3 1.467149 0.00864535 PRICKLE prickle homolog 1 (Drosophila) 1.467122 0.03166895 1 MLLT4 myeloid/lymphoid or mixed-lineage leukemia 1.467081 0.04155191 (trithorax homolog, Drosophila); translocated to, 4 PNPT1 polyribonucleotide nucleotidyltransferase 1 1.466973 0.0270214 NFKB1 nuclear factor of kappa light polypeptide gene 1.466917 0.00255794 enhancer in B-cells 1 DB)/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value VLDLR very low density lipoprotein receptor 1.46686 0.02591 145 XPNPEP2 X-prolyl aminopeptidase (aminopeptidase P) 2, 1.466623 0.02326367 membrane-bound ITPR3 inositol 1,4,5-triphosphate receptor, type 3 1.466453 0.0144499 KIAA092 KIAA0922 1.46645 0.03511673 2 FAM159A family with sequence similarity 159, member A 1.466374 0.04524545 ABCA10 ATP -binding cassette, sub-family A (ABC1), 1.466138 0.00512099 member 10 MRC1 mannose receptor, C type 1 1.466136 0.01757616 TUBGCP tubulin, gamma complex associated protein 5 1.466 0.00886803 5 TMED6 transmembrane emp24 protein transport domain 1.465865 0.03807474 containing 6 BTAF1 BTAF1 RNA polymerase II, B-TFIID 1.46569 0.00731777 transcription factor-associated, 170kDa (Motl homolog, S. cerevisiae) PRG4 Proteoglycan 4 1.465684 0.02402568 SPTY2D1 SPT2, Suppressor of Ty, domain containing 1 (S. 1.465459 0.02139714 cerevisiae) NOL8 nucleolar protein 8 1.465276 0.02289714 ZNF713 zinc finger protein 713 1.465106 0.00024057 GABRG2 gamma-aminobutyric acid (GABA) A receptor, 1.464692 0.02878727 gamma 2 PPIL1 Peptidylprolyl isomerase (cyclophilin)-like 1 1.464672 0.01141798 RXFP4 #N/A 1.46451 0.03271493 SLC30A9 solute carrier family 30 (zinc transporter), member 1.464446 0.01606995 9 A2BP1 #N/A 1.464208 0.01074849 RNF168 ring finger protein 168 1.463842 0.01556207 LARS Leucyl-tRNA synthetase 1.46382 0.0271 1871 AMBRA1 autophagy/beclin-1 regulator 1 1.463678 0.03422866 TUSC3 tumor suppressor candidate 3 1.463532 0.01290509 KLF11 Kruppel-like factor 11 1.463417 0.03410459 ZNF213 zinc finger protein 213 1.463007 0.01 143018 RT34 keratin 34 1.462809 0.04490343 RREB1 ras responsive element binding protein 1 1.462738 0.0215814 QRICH1 glutamine-rich 1 1.462606 0.03381265 SLC41A3 solute carrier family 41, member 3 1.462121 0.04905545 PPID peptidylprolyl isomerase D 1.461711 0.01995451 BRD7 bromodomain containing 7 1.461608 0.03610551 RYK RYK receptor-like tyrosine kinase 1.461366 0.03625633 RMND1 required for meiotic nuclear division 1 homolog 1.461224 0.00067929 (S. cerevisiae) BNIP3L BCL2/adenovirus EIB 19kDa interacting protein 1.460959 0.03837602 3-like NIT2 nitrilase family, member 2 1.460132 0.00731216 AHR aryl hydrocarbon receptor 1.460095 0.01824016 CREG2 cellular repressor of ElA-stimulated genes 2 1.460072 0.04688752 FARS2 phenylalanyl-tRNA synthetase 2, mitochondrial 1.460055 0.01449362 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SLC22A8 solute carrier family 22 (organic anion 1.459997 0.04565017 transporter), member 8 AVPR1A #N/A 1.459881 0.01213536 RDH16 retinol dehydrogenase 16 (all-trans) 1.459701 0.01459158 FOSL2 FOS-like antigen 2 1.459671 0.02789882 CCDC84 coiled-coil domain containing 84 1.459194 0.01551605 C15orf26 chromosome 15 open reading frame 26 1.459144 0.01284189 RNF3 1 ring finger protein 31 1.458904 0.01875917 KIFAP3 kinesin-associated protein 3 1.458765 0.04901628 PvAETlE retinoic acid early transcript IE 1.458688 0.01521063 NFIX nuclear factor I X (CCAAT-binding transcription 1.458648 0.02610177 factor) RRAGD #N/A 1.458582 0.03391708 C2orf37 Chromosome 2 open reading frame 37 1.458512 0.02153276 INE1 #N/A 1.458407 0.04987065 DSN1 DSN1, MIND kinetochore complex component, 1.458314 0.02872824 homolog (S. cerevisiae) CPNE1 copine I 1.458259 0.04343134 FOXJ1 forkhead bo J l 1.45819 0.04892679 KIAA010 #N/A 1.458123 0.011 10807 0 NAV3 neuron navigator 3 1.457858 0.03630539 ZNF4 19 Zinc finger protein 419 1.457487 0.03637576 GPR144 G protein-coupled receptor 144 1.457421 0.0018568 SPTBN5 spectrin, beta, non-erythrocytic 5 1.457323 0.04072569 SLC1A3 solute carrier family 1 (glial high affinity 1.457036 0.00763698 glutamate transporter), member 3 SALL2 sal-like 2 (Drosophila) 1.456788 0.04573085 DLEC1 deleted in lung and esophageal cancer 1 1.456051 0.04460107 MYH3 myosin, heavy chain 3, skeletal muscle, embryonic 1.455842 0.04143603 MAGED4 melanoma antigen family D, 4 1.455781 0.04963849 FAM62C Family with sequence similarity 62 (C2 domain 1.455718 0.00153762 containing), member C C14orf93 chromosome 14 open reading frame 93 1.455704 0.04065932 ALPK3 alpha-kinase 3 1.455636 0.02254821 TWF2 #N/A 1.455423 0.04305335 TPST1 tyrosylprotein sulfotransferase 1 1.455182 0.04488994 TRIM27 tripartite motif-containing 27 1.455008 0.00254227 AOC3 amine oxidase, copper containing 3 (vascular 1.45493 0.00124869 adhesion protein 1) OR7C1 #N/A 1.454841 0.0273752 NR3C1 nuclear receptor subfamily 3, group C, member 1 1.454641 0.02746148 (glucocorticoid receptor) C2orf86 chromosome 2 open reading frame 86 1.454464 0.03587193 MSLN mesothelin 1.454281 0.01815451 COL6A1 collagen, type VI, alpha 1 1.454271 0.04064534 HDHD1A #N/A 1.4541 1 0.01603581 HARS histidyl-tRNA synthetase 1.454047 0.0241 1035 PXK PX domain containing serine/threonine kinase 1.453734 0.02937152 GCLC glutamate-cysteine ligase, catalytic subunit 1.453663 0.02641978 D / 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SS1 L1 synovial sarcoma translocation gene on 1.453659 0.02739503 chromosome 18-like 1 RALYL RALY RNA binding protein-like 1.453082 0.02632547 SYCP1 synaptonemal complex protein 1 1.453082 0.02072635 CCDC69 coiled-coil domain containing 69 1.452643 0.02816828 ALPI alkaline phosphatase, intestinal 1.452631 0.02222572 OPvMl #N/A 1.452285 0.04195743 RFX1 regulatory factor X, 1 (influences HLA class II 1.452074 0.00875266 expression) TNRC6A trinucleotide repeat containing 6A 1.452047 0.02369483 HIP1R huntingtin interacting protein 1 related 1.451914 0.03461542 C2orf44 chromosome 2 open reading frame 44 1.451775 0.04320389 COROIB #N/A 1.451356 0.02900698 COLEC11 #N/A 1.45121 0.04062806 CCDC158 coiled-coil domain containing 158 1.451079 0.021 15158 RNF121 #N/A 1.450747 0.0323907 SCNM1 sodium channel modifier 1 1.450562 0.01556104 ZNF277 zinc finger protein 277 1.45051 0.00702043 MOSPD2 motile sperm domain containing 2 1.450267 0.02091263 ATP5L2 ATP synthase, H+ transporting, mitochondrial F0 1.450265 0.02530962 complex, subunit G2 C9orfl26 Chromosome 9 open reading frame 126 1.450191 0.04664219 CYR61 cysteine-rich, angiogenic inducer, 6 1 1.449852 0.0419131 DNAJC6 DnaJ (Hsp40) homolog, subfamily C, member 6 1.449841 0.02353657 C20orf7 chromosome 20 open reading frame 7 1.449502 0.02641 157 SRRM1 serine/arginine repetitive matrix 1 1.449417 0.01719139 TCF3 transcription factor 3 (E2A immunoglobulin 1.448743 0.04618902 enhancer binding factors E12/E47) LYPD4 LY6/PLAUR domain containing 4 1.448653 0.04099551 STK19 serine/threonine kinase 19 1.448622 0.02320913 ITGAX integrin, alpha X (complement component 3 1.448498 0.01016974 receptor 4 subunit) HISPPD1 Histidine acid phosphatase domain containing 1 1.448177 0.02992748 IL2RG interleukin 2 receptor, gamma (severe combined 1.448103 0.02567381 immunodeficiency) BBC3 BCL2 binding component 3 1.448083 0.04661435 LAMA1 Laminin, alpha 1 1.447955 0.00196975 TIMM44 translocase of inner mitochondrial membrane 44 1.447869 0.00689012 homolog (yeast) KCNV2 potassium channel, subfamily V, member 2 1.447764 0.03217123 C19orf21 #N/A 1.447582 0.0257192 PPM IE protein phosphatase, Mg2+/Mn2+ dependent, IE 1.447264 0.00842577 GLRA1 #N/A 1.447023 0.04108724 ZNF790 zinc finger protein 790 1.446844 0.02823732 VAV1 vav 1 guanine nucleotide exchange factor 1.446454 0.01 174777 ARIH1 ariadne homolog, ubiquitin-conjugating enzyme 1.446394 0.0394967 E2 binding protein, 1 (Drosophila) SYPL1 synaptophysin-like 1 1.446376 0.01547058 MYBPC1 myosin binding protein C, slow type 1.44631 0.00222751 ANKRDl #N/A 1.446181 0.03770147 DB1/ 694 3 7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 6 SGSM3 small G protein signaling modulator 3 1.446031 0.04389755 C2orf3 chromosome 2 open reading frame 3 1.446 0.03568188 LIPH lipase, member H 1.445989 0.02448008 BAT2L #N/A 1.445576 0.04009661 UFY3 RUN and FYVE domain containing 3 1.445443 0.02270059 CCDC78 coiled-coil domain containing 78 1.445173 0.037721 15 HAL histidine ammonia-lyase 1.44516 0.03368006 CALN1 calneuron 1 1.444981 0.01319932 RB1CC1 RBI -inducible coiled-coil 1 1.444531 0.03852258 LDOC1L #N/A 1.444205 0.00918373 SYCP2L synaptonemal complex protein 2-like 1.444066 0.04655165 NLE1 #N/A 1.443846 0.00933605 ME1 malic enzyme 1, NADP(+)-dependent, cytosolic 1.443794 0.04664603 CLIP4 CAP-GLY domain containing linker protein 1.443751 0.03989778 family, member 4 MST1R macrophage stimulating 1 receptor (c-met-related 1.443731 0.0363428 tyrosine kinase) LIN9 lin-9 homolog (C. elegans) 1.443332 0.04299003 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), 1.443182 0.02894376 member 6 C9orf 5 chromosome 9 open reading frame 95 1.443106 0.02650312 ATP6V1C ATPase, H+ transporting, lysosomal 42kDa, VI 1.443098 0.0320308 1 subunit C TYK2 tyrosine kinase 2 1.442974 0.02785366 CNA5 potassium voltage-gated channel, shaker-related 1.442627 0.02893599 subfamily, member 5 FAM90A1 family with sequence similarity 90, member Al 1.44242 0.03069489 NOL10 nucleolar protein 10 1.44239 0.03303329 PMM2 phosphomannomutase 2 1.44225 0.002484 ADD1 adducin 1 (alpha) 1.440954 0.01023506 ACTR3B ARP3 actin-related protein 3 homolog B (yeast) 1.440505 0.04469901 SLC9A1 1 solute carrier family 9, member 11 1.440442 0.00161565 FUT10 Fucosyltransferase 10 (alpha (1,3) 1.440327 0.01438755 fucosyltransferase) PTPRB protein tyrosine phosphatase, receptor type, B 1.440166 0.01445378 STK32B serine/threonine kinase 32B 1.439922 0.03858143 WDR27 WD repeat domain 27 1.439524 0.0262986 CNTNAP contactin associated protein 1 1.439432 0.03843804 1 ZBTB46 zinc finger and BTB domain containing 46 1.439424 0.038251 11 GIMAP5 GTPase, IMAP family member 5 1.438945 0.00841291 CYP3A4 cytochrome P450, family 3, subfamily A, 1.438913 0.01268167 polypeptide 4 USH1C Usher syndrome 1C (autosomal recessive, severe) 1.438859 0.02836779 UBASH3 ubiquitin associated and SH3 domain containing A 1.438688 0.03138061 A RECQL4 RecQ protein-like 4 1.438547 0.0083977 CTNS cystinosis, nephropathic 1.438438 0.04635666 ADAMTS ADAM metallopeptidase with thrombospondin 1.438398 0.03994317 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 20 type 1 motif, 20 UHRF 1BP UHRF 1 binding protein 1-like 1.438167 0.03812257 1L ANKLE 1 #N/A 1.437936 0.04289526 TTC3 1 tetratricopeptide repeat domain 3 1.437808 0.02034163 ZNF555 #N/A 1.437694 0.0221519 PPT1 palmitoyl-protein thioesterase 1 1.437618 0.03650416 MYOIA myosin IA 1.437578 0.00922217 RGL1 #N/A 1.437538 0.03518842 MAP7D2 MAP7 domain containing 2 1.437516 0.04660429 ERO LB ERO 1-like beta (S. cerevisiae) 1.437396 0.04436835 CHML choroideremia-like (Rab escort protein 2) 1.437277 0.01684899 ZNF3 3 zinc finger protein 334 1.437135 0.03342691 CCDC80 coiled-coil domain containing 80 1.436846 0.04107733 DDIT4 DNA-damage-inducible transcript 4 1.436743 0.028691 LRP2 low density lipoprotein receptor-related protein 2 1.436559 0.04792878 HAX 1 HCLS 1 associated protein X-1 1.436401 0.0031628 MPZL1 myelin protein zero-like 1 1.436367 0.02987305 REV1 REV1 homolog (S. cerevisiae) 1.43625 0.01090101 GGPS 1 geranylgeranyl diphosphate synthase 1 1.436175 0.03585913 ZNF5 10 zinc finger protein 510 1.435712 0.01885009 RGS 3 regulator of G-protein signaling 3 1.435473 0.00771751 RNF 185 ring finger protein 185 1.435054 0.04045667 BBS5 Bardet-Biedl syndrome 5 1.43494 0.0399247 NKIRAS 1 NFKB inhibitor interacting Ras-like 1 1.434868 0.041 11426 CHRNB3 #N/A 1.434463 0.03870342 TMOD2 tropomodulin 2 (neuronal) 1.434447 0.01317972 CD163L1 CD1 63 molecule-like 1 1.434359 0.00184705 SHC4 SHC (Src homology 2 domain containing) family, 1.434304 0.01868442 member 4 PHLDA3 pleckstrin homology-like domain, family A, 1.433973 0.03894901 member 3 PPP 3A protein phosphatase 1, regulatory (inhibitor) 1.43373 0.03032323 subunit 3A CCDC79 coiled-coil domain containing 79 1.433536 0.02680449 UGP2 UDP-glucose pyrophosphorylase 2 1.433359 0.01879469 PTPRD protein tyrosine phosphatase, receptor type, D 1.43321 0.02320547 STAG3 stromal antigen 3 1.4331 14 0.02444196 PRRC1 proline-rich coiled-coil 1 1.433027 0.04478808 ARMC8 armadillo repeat containing 8 1.432874 0.04852029 PARP9 poly (ADP-ribose) polymerase family, member 9 1.432814 0.04964132 DTWD2 DTW domain containing 2 1.432515 0.0493533 UNQ6494 QCWQ6494 1.432382 0.02496361 ZMYM4 zinc finger, MYM-type 4 1.432183 0.03154925 C8orf54 chromosome 8 open reading frame 54 1.431962 0.03299928 MTF2 metal response element binding transcription 1.431461 0.04435086 factor 2 UBA5 ubiquitin-like modifier activating enzyme 5 1.431379 0.04616022 C5orf46 chromosome 5 open reading frame 46 1.431223 0.01793586 RNF 9A ring finger protein 9A 1.431067 0.01581715 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value INTS4L1 integrator complex subunit 4-like 1 1.430936 0.02783269 POLR1B polymerase (RNA) I polypeptide B, 128kDa 1.430873 0.01550162 MLH1 mutL homolog 1, colon cancer, nonpolyposis type 1.430761 0.00794245 2 (E. coli) GFM2 G elongation factor, mitochondrial 2 1.430555 0.01383552 ANKRD1 ankyrin repeat domain 17 1.43046 0.04827993 7 FAF1 Fas (TNFRSF6) associated factor 1 1.430 2 1 0.03904638 COX10 #N/A 1.4301 18 0.03538123 C2orf56 chromosome 2 open reading frame 56 1.430048 0.03348655 ZNF19 #N/A 1.429972 0.01649419 MFHAS1 #N/A 1.429933 0.04621658 ZFAND2 zinc finger, AN1 -type domain 2B 1.429775 0.0 1879494 B ADCY2 Adenylate cyclase 2 (brain) 1.429756 0.03216495 EPHA7 EPH receptor A7 1.429676 0.03132041 PAPOLG poly(A) polymerase gamma 1.429616 0.04792028 BCL2L13 BCL2-like 13 (apoptosis facilitator) 1.429059 0.02860466 ARFGAP ADP-ribosylation factor GTPase activating protein 1.428814 0.04525843 1 1 LCORL ligand dependent nuclear receptor corepressor-like 1.428736 0.04488822 NXF4 nuclear RNA export factor 4 pseudogene 1.428667 0.0 1643294 IGHG2 #N/A 1.428576 0.04018687 OVOL2 ovo-like 2 (Drosophila) 1.428425 0.03844006 PTPRZ1 protein tyrosine phosphatase, receptor-type, Z 1.428389 0.04422762 polypeptide 1 SNX2 sorting nexin 2 1.428357 0.04171181 NCOR1 nuclear receptor co-repressor 1 1.427976 0.04923058 C14orf45 Chromosome 14 open reading frame 45 1.427883 0.01624658 SYTL4 synaptotagmin-like 4 1.427768 0.0322787 LDHC #N/A 1.427546 0.03619496 LENG9 leukocyte receptor cluster (LRC) member 9 1.427372 0.02993 145 DCHS1 dachsous 1 (Drosophila) 1.427318 0.0121 132 SLC17A5 solute carrier family 17 (anion/sugar transporter), 1.42719 0.02150945 member 5 TRMU tRNA 5-methylaminomethyl-2-thiouridylate 1.427064 0.01700529 methyltransferase LRRC52 #N/A 1.426523 0.04028452 WDR41 WD repeat domain 4 1.426471 0.00680616 C5orf48 chromosome 5 open reading frame 48 1.426459 0.041 89294 MGC1638 Hypothetical protein MGC 163 85 1.426454 0.02062426 5 C5orf37 Chromosome 5 open reading frame 37 1.425784 0.00637019 MED 19 mediator complex subunit 19 1.425713 0.03386226 DERL2 Deri-like domain family, member 2 1.425344 0.02794415 KLHL30 #N/A 1.4249 0.04129442 C22orf43 #N/A 1.424794 0.04583136 ACTL6A actin-like 6A 1.42451 0.04623304 ALOX5A #N/A 1.424267 0.00272828

DB1/ 69437516.I Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value LTBP1 latent transforming growth factor beta binding 1.424099 0.04996473 protein 1 SPG11 Spastic paraplegia 11 (autosomal recessive) 1.423899 0.03021 136 NXF3 nuclear RNA export factor 3 1.423693 0.03537481 LAMA4 laminin, alpha 4 1.423591 0.04403999 SLC26A1 Solute carrier family 26, member 11 1.423394 0.0442195 1 MOBKL1 MOBl, Mps One Binder kinase activator-like 1A 1.423253 0.02598551 A (yeast) IL8 #N/A 1.423252 0.03879855 EIF2AK1 eukaryotic translation initiation factor 2-alpha 1.42324 0.02190845 kinase 1 RBPMS RNA binding protein with multiple splicing 1.422673 0.041 19182 BRE brain and reproductive organ-expressed 1.422448 0.02514955 (TNFRSF1 A modulator) NCK1 NCK adaptor protein 1 1.422439 0.03578054 DRAP1 #N/A 1.422065 0.03621038 RUNDC3 RUN domain containing 3B 1.421857 0.04330288 B SYNJ2BP #N/A 1.421739 0.02283196 PDE7B phosphodiesterase 7B 1.421678 0.03688497 PDK1 pyruvate dehydrogenase kinase, isozyme 1 1.421279 0.03042126 SLC28A3 solute carrier family 28 (sodium-coupled 1.420863 0.04586862 nucleoside transporter), member 3 DPM2 dolichyl-phosphate mannosyltransferase 1.42053 0.00599389 polypeptide 2, regulatory subunit SCYL1 SCYl-like 1 (S. cerevisiae) 1.42052 0.04474295 C6orfl65 chromosome 6 open reading frame 165 1.420502 0.00218418 KIR3DL1 killer cell immunoglobulin-like receptor, three 1.420189 0.0136071 1 domains, long cytoplasmic tail, 1 SLC25A3 solute carrier family 25 (mitochondrial carrier; 1.420003 0.02483151 phosphate carrier), member 3 ZNF212 #N/A 1.419877 0.0251 1564 ACSBG2 acyl-CoA synthetase bubblegum family member 2 1.419763 0.04014889 LEKR1 #N/A 1.419752 0.04682436 MTUS1 microtubule associated tumor suppressor 1 1.418787 0.03798287 MY01B myosin IB 1.418658 0.00197662 MIOX #N/A 1.418575 0.04954692 ALS2CR4 amyotrophic lateral sclerosis 2 (juvenile) 1.418546 0.0310462 chromosome region, candidate 4 DI03 deiodinase, iodothyronine, type III 1.418513 0.00819247 CALCB #N/A 1.418355 0.00838483 ME2 malic enzyme 2, NAD(+)-dependent, 1.418274 0.01841145 mitochondrial CAGE1 cancer antigen 1 1.418164 0.03913329 GPBP1L1 GC-rich promoter binding protein 1-like 1 1.418033 0.04799429 PLA2R1 phospholipase A2 receptor 1, 180kDa 1.417542 0.00923605 GPSM1 G-protein signaling modulator 1 (AGS3-like, C. 1.417471 0.04785931 elegans) CHP2 calcineurin B homologous protein 2 1.41739 0.04969681 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value NUMB numb homolog (Drosophila) 1.417215 0.02478936 AOC2 amine oxidase, copper containing 2 (retina- 1.417046 0.01426703 specific) TRERF transcriptional regulating factor 1 1.416101 0.03254844 RAPGEFl Rap guanine nucleotide exchange factor (GEF) 1 1.415895 0.04265785 CTH cystathionase (cystathionine gamma-lyase) 1.415796 0.0428465 PCDH24 #N/A 1.415716 0.0291154 PISD #N/A 1.415277 0.03084606 TTC25 tetratricopeptide repeat domain 25 1.415135 0.00096534 DIP2C DIP2 disco-interacting protein 2 homolog C 1. 15117 0.03521672 (Drosophila) KCNK17 potassium channel, subfamily K, member 1 1.415067 0.04872156 CPS1 carbamoyl-phosphate synthase 1, mitochondrial 1.415049 0.02220611 LSM12 #N/A 1.414925 0.04599678 RDH10 #N/A 1.4149 0.0303362 PIP5K1C phosphatidylinositol-4-phosphate 5-kinase, type I, 1.414862 0.03680471 gamma AGRP #N/A 1.414749 0.03624587 KISS1R KISS1 receptor 1.414596 0.04660972 CEP170L #N/A 1.414297 0.00533912 TFB2M transcription factor B2, mitochondrial 1.414276 0.00766602 ARAP3 ArfGAP with RhoGAP domain, ankyrin repeat 1.414139 0.04810273 and PH domain 3 ATP6V1G ATPase, H+ transporting, lysosomal 13kDa, V I 1.413912 0.01696754 2 subunit G2 OR51F1 #N/A 1.413838 0.02868178 ARFIP2 ADP-ribosylation factor interacting protein 2 1.4 13806 0.00699041 GTF3C3 general transcription factor IIIC, polypeptide 3, 1.413757 0.03007023 102kDa PRDM15 PR domain containing 15 1.413293 0.03857759 MPDZ multiple PDZ domain protein 1.413148 0.00731358 FXR2 fragile X mental retardation, autosomal homolog 2 1.413137 0.04479532 CLEC1A #N/A 1.412984 0.0237952 HADH #N/A 1.412827 0.01477945 FRAP 1 FK506 binding protein 12-rapamycin associated 1.41 2768 0.03216416 protein 1 TAPBP TAP binding protein (tapasin) 1.41 2705 0.01852405 GPR126 G protein-coupled receptor 126 1.412461 0.03202184 VEPH1 ventricular zone expressed PH domain homolog 1 1.412406 0.04250664 (zebrafish) DDB damage-specific DNA binding protein 1, 127kDa 1. 1234 0.0326726 PODN podocan 1.412215 0.02049473 C14orfl77 chromosome 14 open reading frame 177 1.412036 0.01060699 NADK NAD kinase 1.41 1726 0.04453067 PRKACB protein kinase, cAMP-dependent, catalytic, beta 1.41 1632 0.04890563 MRGPRX #N/A 1.41 157 0.04440184 1 LASS1 LAG1 homolog, ceramide synthase 1 1.41 1301 0.03143383 CA11 carbonic anhydrase XI 1.41 1239 0.02467048 TAF7L TAF7-like RNA polymerase II, TATA box 1. 168 0.03198948 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value binding protein (TBP)-associated factor, 50kDa LOC1586 hypothetical LOCI 58696 1.41 1086 0.02489639 96 SPEF2 sperm flagellar 2 1.411013 0.01013766 SAMD4A sterile alpha motif domain containing 4A 1.410742 0.03063432 C8orf44 #N/A 1.410533 0.01332613 HIST1H3J histone cluster 1, H3j 1.410359 0.00103398 PON2 paraoxonase 2 1.410181 0.02722414 ZNF71 #N/A 1.410135 0.04534524 BTNL8 butyrophilin-like 8 1.410086 0.02585348 PEX16 #N/A 1.409984 0.01029936 EYA1 eyes absent homolog 1 (Drosophila) 1.409781 0.01320983 FAM54B family with sequence similarity 54, member B 1.409645 0.00862757 BRD3 #N/A 1.409586 0.00784168 LOC7282 #N/A 1.409519 0.04143559 12 SPEG #N/A 1.409468 0.00375427 TBRG4 #N/A 1.40939 0.02950791 ROPN1B #N/A 1.408993 0.00790338 SNAP47 synaptosomal-associated protein, 47kDa 1.408485 0.04602921 AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 1.408331 0.0397578 TIGD5 tigger transposable element derived 5 1.408267 0.020565 C14orf79 chromosome 14 open reading frame 79 1.408188 0.03685775 C8orf79 Chromosome 8 open reading frame 79 1.40808 0.01438085 ZBED4 zinc finger, BED-type containing 4 1.407985 0.01114324 PTPN12 protein tyrosine phosphatase, non-receptor type 12 1.407633 0.04343223 FAM91A1 family with sequence similarity 91, member Al 1.407477 0.01878871 G2E3 G2/M-phase specific E3 ubiquitin ligase 1.407412 0.0340295 GALNT8 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.407377 0.00638373 N-acetylgalactosaminyltransferase 8 (GalNAc-T8) ANGPT1 #N/A 1.407237 0.04946848 ADRBK2 adrenergic, beta, receptor kinase 2 1.407184 0.03936594 TTLL10 tubulin tyrosine ligase-like family, member 0 1.407102 0.03185513 LPHN2 latrophilin 2 1.406759 0.03075214 POLR2C polymerase (RNA) II (DNA directed) polypeptide 1.406734 0.01483067 C, 3 kDa GON4L gon-4-like (C. elegans) 1.406578 0.02792844 TJP2 tight junction protein 2 (zona occludens 2) 1.406495 0.041951 12 CLEC4C #N/A 1.406452 0.01047827 CD34 CD34 molecule 1.406256 0.02143454 EIF4G3 eukaryotic translation initiation factor 4 gamma, 3 1.406204 0.00853982 KCMF1 potassium channel modulatory factor 1 1.406049 0.03966502 NLGN4X neuroligin 4, X-linked 1.405981 0.04808391 SYT4 #N/A 1.405821 0.02588059 PGAP1 post-GPI attachment to proteins 1 1.40579 0.04981905 HCRTR2 hypocretin (orexin) receptor 2 1.405277 0.04487237 MBD3L1 #N/A 1.405222 0.00721026 ERCC4 excision repair cross-complementing rodent repair 1.405166 0.04499256 deficiency, complementation group 4 KRTAP13 #N/A 1.404759 0.0428822 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value - 1 TRNAU1 tRNA selenocysteine 1 associated protein 1 1.404681 0.0431 1386 AP IPO 11 importin 1 1.404451 0.04851699 C16orf52 Chromosome 16 open reading frame 52 1.404438 0.03309352 CPXM2 carboxypeptidase X (Ml 4 family), member 2 1.40407 0.02406586 ARPC2 actin related protein 2/3 complex, subunit 2, 1.403844 0.04550945 34kDa FAM129C family with sequence similarity 129, member C 1.403626 0.0330672 RABGEF RAB guanine nucleotide exchange factor (GEF) 1 1.403497 0.03434929 1 TCEB3 transcription elongation factor B (SIII), 1.403204 0.03240308 polypeptide 3 ( 1lOkDa, elongin A) RYR2 ryanodine receptor 2 (cardiac) 1.403032 0.03605059 GHDC GH3 domain containing 1.402837 0.01882408 SERTAD4 SERTA domain containing 4 1.402681 0.00359257 KCNT2 Potassium channel, subfamily T, member 2 1.402521 0.04560752 CLSPN claspin homolog (Xenopus laevis) 1.402502 0.02545263 MOCS1 molybdenum cofactor synthesis 1 1.402262 0.00758675 DCT #N/A 1.402217 0.01437619 NLRP9 NLR family, pyrin domain containing 9 1.402215 0.04470192 CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.402206 0.03725548 D4 subunit 4 SLC25A3 solute carrier family 25 (mitochondrial carrier; 1.402178 0.03455203 1 adenine nucleotide translocator), member 31 ALDH4A aldehyde dehydrogenase 4 family, member A l 1.402143 0.0428196 1 ZNF12 zinc finger protein 1.402106 0.02420556 MYL4 myosin, light chain 4, alkali; atrial, embryonic 1.401793 0.02323071 CELP carboxyl ester lipase pseudogene 1.401509 0.04098698 OLFML2 olfactomedin-like 2B 1.40142 0.03843012 B DPY19L2 dpy-19-like 2 (C. elegans) 1.401349 0.03991465 CCDC48 coiled-coil domain containing 48 1.401291 0.02399671 WDR60 WD repeat domain 60 1.401204 0.01727148 MDGA1 MAM domain containing 1.400745 0.03911931 glycosylphosphatidylinositol anchor 1 CCDC150 coiled-coil domain containing 150 1.400713 0.00923587 SLC38A9 solute carrier family 38, member 9 1.40062 0.03176665 FRMPD2 FERM and PDZ domain containing 2 1.40054 0.00373957 ABTB2 ankyrin repeat and BTB (POZ) domain containing 1.400178 0.0245051 2 UPB1 ureidopropionase, beta 1.399598 0.02286101 TSN translin 1.399509 0.03659249 WASF1 WAS protein family, member 1 1.399399 0.01274934 PIGO phosphatidylinositol glycan anchor biosynthesis, 1.398797 0.04188742 class O C7orf29 #N/A 1.398712 0.03424425 RHPN1 rhophilin, Rho GTPase binding protein 1 1.39868 0.01520561 COR02A #N/A 1.398661 0.03986101 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ACSM3 acyl-CoA synthetase medium-chain family 1.398465 0.01871956 member 3 D4S234E DNA segment on chromosome 4 (unique) 234 1.398344 0.04212178 expressed sequence ATP1 1B ATPase, class VI, type 1IB 1.398172 0.04591405 TCOF1 Treacher Collins-Franceschetti syndrome 1 1.398069 0.0391 157 GALT galactose- 1-phosphate uridylyltransferase 1.397966 0.00247261 HRG histidine-rich glycoprotein 1.397856 0.03777067 R AG #N/A 1.39752 0.03485837 LOC6469 twelve-thirteen translocation leukemia gene 1.397169 0.00873384 82 AUP1 ancient ubiquitous protein 1 1.396355 0.02026702 PHF3 PHD finger protein 3 1.39621 1 0.01054891 RGPD5 RANBP2-like and GRIP domain containing 5 1.396117 0.04893838 S100A14 #N/A 1.396006 0.0066653 HSD17B1 hydroxysteroid (17-beta) dehydrogenase 11 1.395945 0.03304075 1 CACNA1 calcium channel, voltage-dependent, T type, alpha 1.395622 0.03864677 H 1H subunit TRIM68 #N/A 1.395566 0.04779924 SCN10A sodium channel, voltage-gated, type X, alpha 1.395546 0.03812938 subunit SPAG17 sperm associated antigen 17 1.395519 0.0299796 KRT20 keratin 20 1.395271 0.03217697 DGAT2L6 diacylglycerol O-acyltransferase 2-like 6 1.395177 0.02714545 MS4A10 Membrane-spanning 4-domains, subfamily A, 1.394905 0.0318291 member 10 POSTN periostin, osteoblast specific factor 1.394528 0.00856569 CLEC4G #N/A 1.394409 0.01651661 LQK1 LQK1 hypothetical protein short isoform 1.39403 0.02557725 FM04 #N/A 1.393464 0.02372092 CABP2 #N/A 1.393445 0.04869489 CD83 CD83 molecule 1.393225 0.03750887 RAB39B #N/A 1.3926 0.00729975 C10orf58 #N/A 1.392475 0.0313261 UBC #N/A 1.39239 0.04488279 SLC3A1 solute carrier family 3 (cystine, dibasic and neutral 1.392282 0.03412927 amino acid transporters, activator of cystine, dibasic and neutral amino acid transport), member 1 1 SEPP1 selenoprotein P, plasma, 1 1.392278 0.01276165 HRC histidine rich calcium binding protein 1.392189 0.02392761 NCSTN nicastrin 1.39212 0.03276348 PER3 period homolog 3 (Drosophila) 1.391761 0.04590857 ITGB8 integrin, beta 8 1.391437 0.01007626 G3BP2 GTPase activating protein (SH3 domain) binding 1.391061 0.03995435 protein 2 DMBT1 deleted in malignant brain tumors 1 1.391016 0.01095332 ERBB2IP erbb2 interacting protein 1.390929 0.00826632 NCRNAO non-protein coding RNA 174 1.390833 0.01828585 1/694375 6.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 0174 ABCA3 #N/A 1.390303 0.04042122 ARMC3 armadillo repeat containing 3 1.3901 7 0.0241 8 78 GAA glucosidase, alpha; acid 1.390145 0.02416388 WDR16 WD repeat domain 16 1.389763 0.00382488 MAP3K7 mitogen-activated protein kinase kinase kinase 7 1.389714 0.01863856 WDR35 WD repeat domain 35 1.38932 0.03314722 TTF1 transcription termination factor, RNA polymerase 1.38918 0.01861324 I EHMT2 euchromatic histone-lysineN-methyltransferase 2 1.389037 0.04529926 SP140L SP140 nuclear body protein-like 1.388923 0.0361833 CUL2 cullin 2 1.388834 0.03417199 PDYN prodynorphin 1.388793 0.01792923 GSK3B glycogen synthase kinase 3 beta 1.388704 0.0 1324586 DDX59 DEAD (Asp-Glu- Ala-Asp) box polypeptide 59 1.38866 0.01 161362 FEZ2 fasciculation and elongation protein zeta 2 (zygin 1.388464 0.01625731 Π) NUAK2 NUAK family, SNFl-like kinase, 2 1.388457 0.00947788 ITLN2 intelectin 2 1.388199 0.04185219 RNF149 ring finger protein 149 1.388136 0.03753609 ZFYVE20 zinc finger, FYVE domain containing 20 1.388131 0.0368595 1 PIWIL3 Piwi-like 3 (Drosophila) 1.388125 0.04611083 ZNF230 zinc finger protein 2 0 1.388118 0.01064806 RAB27B RAB27B, member RAS oncogene family 1.387967 0.0450371 RRP9 ribosomal RNA processing 9, small subunit (SSU) 1.38781 0.02464482 processome component, homolog (yeast) C17orf53 chromosome 17 open reading frame 53 1.38774 0.0078672 2-Sep #N/A 1.387431 0.03338744 FUCA1 fucosidase, alpha-L- , tissue 1.38741 0.02925501 PDCD11 programmed cell death 11 1.387102 0.04328171 CATSPER Cation channel, sperm associated 2 pseudogene 1 1.386958 0.03847495 2P1 FLJ44881 FLJ44881 1.386885 0.04903313 SNAPC5 #N/A 1.386849 0.00725544 C20orf71 chromosome 20 open reading frame 7 1 1.386461 0.04746647 CNIP2 Kv channel interacting protein 2 1.386433 0.03326746 BMP2K BMP2 inducible kinase 1.386192 0.04872796 NR2E3 nuclear receptor subfamily 2, group E, member 3 1.386135 0.0494817 HEYL hairy/enhancer-of-split related with YRPW m otif 1.386075 0.03114455 like ATP5D #N/A 1.386046 0.03800337 STAP2 #N/A 1.385918 0.04606399 ACAT2 acetyl-CoA acetyltransferase 2 1.385302 0.02677085 CCDC17 coiled-coil domain containing 17 1.385042 0.04001854 PIN1L peptidylprolyl cis/trans isomerase, NIMA- 1.384965 0.04185282 interacting 1-like (pseudogene) KIAA1 19 KIAA1191 1.38493 0.02319146 1 FLOT1 flotillin 1 1.384924 0.03926247 FAM83C family with sequence similarity 83, member C 1.384922 0.03647672 D / 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value RFXANK regulatory factor X-associated ankyrin-containing 1.384612 0.03248029 protein JARID2 jumonji, AT rich interactive domain 2 1.384407 0.00690906 PIK3CG phosphoinositide-3 -kinase, catalytic, gamma 1.384287 0.01670825 polypeptide EXOC3L2 exocyst complex component 3-like 2 1.384174 0.03521837 PDXK pyridoxal (pyridoxine, vitamin B6) kinase 1.384091 0.03873832 MAGEB1 melanoma antigen family B, 1 1.383909 0.01558786 C5 complement component 5 1.38387 0.01555144 CASKIN2 CASK interacting protein 2 1.383695 0.00978574 PYCRL pyrroline-5-carboxylate reductase-like 1.383376 0.02332003 CTDP1 CTD (carboxy-terminal domain, RNA polymerase 1.3832 0.02699086 II, polypeptide A) phosphatase, subunit 1 PRDX1 peroxiredoxin 1 1.38319 0.0314545 LASS2 LAG1 homolog, ceramide synthase 2 1.383183 0.01736726 FAM83A family with sequence similarity 83, member A 1.383114 0.02272562 ADAD2 adenosine deaminase domain containing 2 1.382822 0.0290104 ZYG1 1B zyg-1 1 homolog B (C. elegans) 1.382759 0.03637639 DGCR8 DiGeorge syndrome critical region gene 8 1.382451 0.01673764 SLC2A5 solute carrier family 2 (facilitated glucose/fructose 1.382214 0.02054184 transporter), member 5 CXorf22 chromosome X open reading frame 22 1.382178 0.02367145 GDAP2 ganglioside induced differentiation associated 1.381444 0.02555595 protein 2 PITX2 #N/A 1.38095 0.03603224 FARP2 FERM, RhoGEF and pleckstrin domain protein 2 1.380538 0.0362369 C4orf8 Chromosome 4 open reading frame 8 1.380393 0.04410986 DCP2 DCP2 decapping enzyme homolog (S. cerevisiae) 1.380372 0.02782318 RAB2A RAB2A, member RAS oncogene family 1.38031 0.02989203 SNX17 #N/A 1.38031 0.04778598 BLID #N/A 1.379936 0.04489691 FLJ26850 FLJ26850 protein 1.379795 0.0315004 SLC12A2 solute carrier family 12 1.379717 0.01203849 (sodium/potassium/chloride transporters), member

PHKA2 phosphorylase kinase, alpha 2 (liver) 1.379358 0.04156652 MAD2L1 N/A 1.379319 0.02498422 BP PUS10 pseudouridylate synthase 10 1.37928 0.03260097 GRHL1 grainyhead-like 1 (Drosophila) 1.379134 0.04726898 ARIH2 ariadne homolog 2 (Drosophila) 1.379092 0.04036547 SOX21 SRY (sex determining region Y)-box 2 1 1.379007 0.03381278 MAMDC2 MAM domain containing 2 1.378926 0.03908725 PLA2G2A phospholipase A2, group IIA (platelets, synovial 1.37892 0.02830803 fluid) NGFRAP nerve growth factor receptor (TNFRSF16) 1.378697 0.03131 156 1 associated protein 1 SFTPA1 surfactant protein A l 1.378651 0.04576467 EML3 echinoderm microtubule associated protein like 3 1.378484 0.02696298 GSDMB gasdermin B 1.37845 0.04470307 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value Clorf83 chromosome 1 open reading frame 83 1.377876 0.03773114 R F14 ring finger protein 14 1.377805 0.04782365 SAT1 spermidine/spermine Nl-acetyltransferase 1 1.377678 0.0199371 TAF1L TAF1 RNA polymerase II, TATA box binding 1.377677 0.01341919 protein (TBP)-associated factor, 210kDa-like AMT aminomethyltransferase 1.377596 0.04610355 TARSL2 threonyl-tRNA synthetase-like 2 1.37744 0.03384658 KCNMB1 N/A 1.377197 0.01536732 EFNA5 ephrin-A5 1.376946 0.02612841 ULK1 unc-51-like kinase 1 (C. elegans) 1.376606 0.04913687 TESSP5 #N/A 1.376448 0.00800435 SOCS5 suppressor of cytokine signaling 5 1.37553 0.01917031 CLPX ClpX caseinolytic peptidase X homolog (E. coli) 1.375441 0.01468959 LNX2 Ligand of numb-protein X 2 1.375437 0.04247097 GLS glutaminase 1.375186 0.03479203 BMP4 bone morphogenetic protein 4 1.375126 0.01823714 EBF4 early B-cell factor 4 1.374912 0.03180139 SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.374893 0.04735748 SERPINB serpin peptidase inhibitor, clade B (ovalbumin), 1.374614 0.04079695 13 member 13 CYBA cytochrome b-245, alpha polypeptide 1.374566 0.01905461 SECISBP SECIS binding protein 2-like 1.374566 0.04433205 2L CLCNKA chloride channel Ka 1.374472 0.03583901 TM7SF4 transmembrane 7 superfamily member 4 1.37444 0.04083846 FLJ40852 #N/A 1.374363 0.04940007 C6orf54 #N/A 1.374323 0.02034623 HIF3A Hypoxia inducible factor 3, alpha subunit 1.3743 0.03370266 CGNL1 cingulin-like 1 1.374127 0.02383984 C14orf49 chromosome 14 open reading frame 49 1.374057 0.0211786 RHOBTB Rho-related BTB domain containing 3 1.373996 0.01988465 3 ELP3 elongation protein 3 homolog (S. cerevisiae) 1.373642 0.03955407 POLR2H polymerase (RNA) II (DNA directed) polypeptide 1.373227 0.02984487 H KIAA131 KIAA1310 1.373158 0.04142218 0 SLC35A1 solute carrier family 35 (CMP-sialic acid 1.372979 0.0029421 transporter), member Al NCRNAO non-protein coding RNA 175 1.372758 0.00985385 0175 C lorf35 #N/A 1.372583 0.04741799 FEZF2 FEZ family zinc finger 2 1.372156 0.01753083 NCKAP1 NCK-associated protein 1 1.3721 16 0.02620886 9-Sep #N/A 1.371851 0.04857443 RTP4 #N/A 1.371731 0.04756939 CFTR cystic fibrosis transmembrane conductance 1.371604 0.03587373 regulator (ATP-binding cassette sub-family C, member 7) ST14 suppression of tumorigenicity 14 (colon 1.371459 0.03200038 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value carcinoma) AP3S1 adaptor-related protein complex 3, sigma 1 subunit 1.37125 0.0071826 FAM49B family with sequence similarity 49, member B 1.37124 0.04761414 SMARCA SWI/SNF related, matrix associated, actin 1.371225 0.01914396 2 dependent regulator of chromatin, subfamily a, member 2 ACBD4 acyl-CoA binding domain containing 4 1.37122 0.03423982 EFCAB6 EF-hand calcium binding domain 6 1.370919 0.04000618 XAGE2 #N/A 1.370913 0.03807452 CTSS cathepsin S 1.370682 0.01961639 DOK5 docking protein 5 1.37065 0.00588661 ZNF3 zinc finger protein 3 1.370646 0.02001535 AN04 anoctamin 4 1.370627 0.04972677 ZBTB48 zinc finger and BTB domain containing 48 1.370607 0.00410921 TMEM 8 transmembrane protein 183B 1.370591 0.04077533 3B HDLBP high density lipoprotein binding protein 1.370587 0.02901277 SPAG7 sperm associated antigen 7 1.370365 0.04772279 QPCT glutaminyl -peptide cyclotransferase 1.370054 0.04693999 WDR33 WD repeat domain 33 1.369404 0.02111859 GPR132 #N/A 1.36932 0.04152648 KRT15 keratin 15 1.369198 0.02838278 EPS8L1 EPS8-like 1 1.368955 0.01719425 RGS5 #N/A 1.368892 0.01376485 MFAP3L microfibrillar-associated protein 3-like 1.368818 0.04260298 CLCA2 chloride channel accessory 2 1.368776 0.04106998 ATHL1 ATH1, acid trehalase-like 1 (yeast) 1.368744 0.00844971 USP6 ubiquitin specific peptidase 6 (Tre-2 oncogene) 1.36864 0.02369601 LZTFL1 leucine zipper transcription factor-like 1 1.368487 0.02321085 HSF4 #N/A 1.368486 0.04389483 BPY2 basic charge, Y-linked, 2 1.368245 0.04532575 CASS4 Cas scaffolding protein family member 4 1.368237 0.04868791 KLHL 10 kelch-like 0 (Drosophila) 1.368113 0.04173072 IL4R interleukin 4 receptor 1.367682 0.04745193 UQCRH ubiquinol-cytochrome c reductase hinge protein 1.367633 0.04991558 GALNT10 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.367612 0.01578419 N-acetylgalactosaminyltransferase 10 (GalNAc- T10) SESTD1 SEC 14 and spectrin domains 1 1.366888 0.03597631 PPFIA2 protein tyrosine phosphatase, receptor type, f 1.366368 0.00766609 polypeptide (PTPRF), interacting protein (liprin), alpha 2 EIF3M eukaryotic translation initiation factor 3, subunit M 1.366228 0.02809051 CDH1 8 cadherin 18, type 2 1.366148 0.00125786 SF3B1 splicing factor 3b, subunit 1, 155kDa 1.365473 0.04469656 ZMAT1 #N/A 1.36442 0.02781449 KCNJ14 potassium inwardly-rectifying channel, subfamily 1.364123 0.0248093 J, member 14 PALLD palladin, cytoskeletal associated protein 1.363762 0.04986509 ΓΝΡΡ4Β inositol polyphosphate-4-phosphatase, type II, 1.363494 0.00017936 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 105kDa ABCB5 ATP-binding cassette, sub-family B (MDR/TAP), 1.363481 0.01402067 member 5 TFRC transferrin receptor (p90, CD71) 1.363435 0.02452106 Clorfl22 chromosome 1 open reading frame 122 1.363401 0.03699855 PTH #N/A 1.363071 0.02032375 ZNF 1 #N/A 1.362871 0.03284971 AEBP2 AE binding protein 2 1.362569 0.03985048 KIAA180 mixed lineage kinase 4 1.362362 0.00777953 4 ACSL5 acyl-CoA synthetase long-chain family member 5 1.362342 0.03073901 TNIP1 TNFAIP3 interacting protein 1 1.362235 0.02962173 HIST1H4 #N/A 1.362152 0.00134079 D F8 coagulation factor VIII, procoagulant component 1.36153 0.0330432 RFX4 regulatory factor X, 4 (influences HLA class II 1.361522 0.03667079 expression) CLEC1B #N/A 1.361151 0.02599373 C4orf30 Chromosome 4 open reading frame 30 1.35993 0.03562827 RHCE #N/A 1.359475 0.03662927 KIAA196 KIAA1967 1.359378 0.0188366 7 LYN v-yes-1 Yamaguchi sarcoma viral related 1.359373 0.01200334 oncogene homolog RPS6KA6 ribosomal protein S6 kinase, 90kDa, polypeptide 6 1.359313 0.01574272 KIRREL2 Kin of IRRE like 2 (Drosophila) 1.359171 0.04649818 TR1M14 tripartite motif-containing 14 1.359063 0.04936092 GPBP1 GC-rich promoter binding protein 1 1.359053 0.03480641 CGREF1 #N/A 1.358723 0.01457688 ZNF79 zinc finger protein 79 1.358718 0.04549962 HHIPL2 HHIP-like 2 1.358436 0.03833599 GRIN2B #N/A 1.358397 0.0075932 CATSPER cation channel, sperm associated 1 1.358087 0.03085318 1 AHNAK2 AHNAK nucleoprotein 2 1.357789 0.01594685 CXCL13 chemokine (C-X-C motif) ligand 1 1.357676 0.00878467 GTF2IRD GTF2I repeat domain containing 2 pseudogene 1.35742 0.04895984 2P PCMT1 protein-L-isoaspartate (D-aspartate) O- 1.357331 0.00986394 methyltransferase INPP5D inositol polyphosphate-5 -phosphatase, 145kDa 1.357218 0.03501015 ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit 1.357003 0.03979787 of VLA-4 receptor) SPAST spastin 1.356288 0.03786354 PRLH prolactin releasing hormone 1.356089 0.02371997 UTP6 UTP6, small subunit (SSU) processome 1.356011 0.03536297 component, homolog (yeast) PKD2 polycystic kidney disease 2 (autosomal dominant) 1.355906 0.03251514 SUGT1L1 SGT1, suppressor of G2 allele of SKP1 like 1 (S. 1.35567 0.00885436 cerevisiae) 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value MFI2 antigen p97 (melanoma associated) identified by 1.355647 0.00363659 monoclonal antibodies 133.2 and 96.5 TMEM14 transmembrane protein 146 1.355608 0.02720724 6 TTTY6 testis-specific transcript, Y-linked 6 (non-protein 1.355107 0.0474792 coding) ΓΠΗ3 inter-alpha (globulin) inhibitor H3 1.354798 0.02342705 ILDR1 immunoglobulin-like domain containing receptor 1.354615 0.02734741 1 MY018A myosin XVIIIA 1.354563 0.0434213 RIC8B resistance to inhibitors of cholinesterase 8 1.35437 0.03801956 homolog B (C. elegans) CTN A3 Catenin (cadherin-associated protein), alpha 3 1.354368 0.03510529 GREB1 GREB1 protein 1.354247 0.04230805 KDM3B lysine (K)-specific demethylase 3B 1.35412 0.04179252 VIT #N/A 1.35379 0.02402971 NECAB2 N-terminal EF-hand calcium binding protein 2 1.353677 0.04090459 B4GALN beta-l,4-N-acetyl-galactosaminyl transferase 1 1.353321 0.00575749 Tl PSMB7 #N/A 1.353301 0.04033224 TOPORS Topoisomerase I binding, arginine/serine-rich 1.353172 0.00192257 MAPK8 mitogen-activated protein kinase 8 1.352867 0.03733872 A2M alpha-2-macroglobulin 1.352659 0.01926322 PSMA7 proteasome (prosome, macropain) subunit, alpha 1.35225 0.03229301 type, 7 7-Mar #N/A 1.352115 0.00153926 RABGGT Rab geranylgeranyltransferase, alpha subunit 1.351954 0.0429941 A S100A3 #N/A 1.351681 0.01844129 PGDS #N/A 1.351548 0.02579275 POLR3GL polymerase (RNA) III (DNA directed) polypeptide 1.351326 0.04224969 G (32kD)-like PSTK phosphoseryl-tRNA kinase 1.35128 0.04649495 CEP350 centrosomal protein 350kDa 1.351128 0.03670049 KDM4C lysine (K)-specific demethylase 4C 1.351053 0.0176246 ACY1 aminoacylase 1 1.35078 0.00373775 RNF32 ring finger protein 32 1.350722 0.04810592 BMX BMX non-receptor tyrosine kinase 1.350412 0.03189594 ZNF804A zinc finger protein 804A 1.350319 0.015929 RPH3A rabphilin 3A homolog (mouse) 1.349799 0.01617809 TARS threonyl-tRNA synthetase 1.349756 0.04996272 GPR133 G protein-coupled receptor 133 1.349679 0.02919616 Clorfl04 chromosome 1 open reading frame 104 1.349616 0.01600065 CATSPER cation channel, sperm associated 2 1.349606 0.03144666 2 FNBP4 formin binding protein 4 1.349354 0.00845931 MCM6 minichromosome maintenance complex 1.349263 0.03160563 component 6 SLC27A1 Solute carrier family 27 (fatty acid transporter), 1.349238 0.01250896 member 1 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Unregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PHC1 polyhomeotic homolog 1 (Drosophila) 1.34907 0.04242083 PIN 1 PTEN induced putative kinase 1 1.348951 0.03249442 TP 1 thiamin pyrophosphokinase 1 1.348935 0.00061583 KRTAP1- #N/A 1.348868 0.02700125 5 KIR2DL1 killer cell immunoglobulin-like receptor, two 1.348833 0.04699831 domains, long cytoplasmic tail, 1 DSP desmoplakin 1.348754 0.04651279 MREl 1A MREl 1 meiotic recombination 11 homolog A (S. 1.348564 0.00038333 cerevisiae) SPAG9 sperm associated antigen 9 1.348534 0.03303382 CCDC11 coiled-coil domain containing 11 1.34835 0.04368236 ATP7B ATPase, Cu++ transporting, beta polypeptide 1.348154 0.03209184 WDR92 #N/A 1.347904 0.0438393 ITGB1BP integrin beta 1 binding protein 3 1.347859 0.00957784 3 BLMH bleomycin hydrolase 1.347696 0.03973197 PKD1L1 polycystic kidney disease 1 like 1 1.34761 0.01490888 PECR peroxisomal trans-2-enoyl-CoA reductase 1.347163 0.02598704 DNAH5 dynein, axonemal, heavy chain 5 1.346943 0.0280359 ZNF566 zinc finger protein 566 1.346867 0.00318496 CXorf26 chromosome X open reading frame 26 1.346699 0.01655183 ATXN7L2 ataxin 7-like 2 1.346592 0.02446553 HM13 #N/A 1.346496 0.03424705 PREPL prolyl endopeptidase-like 1.346456 0.03536804 MAST1 microtubule associated serine/threonine kinase 1 1.345867 0.01970894 PLRG1 pleiotropic regulator 1 (PRL1 homolog, 1.345685 0.00188631 Arabidopsis) ETV7 ets variant 7 1.345592 0.00259091 MAGEF1 melanoma antigen family F, 1 1.345586 0.0427293 NELL1 NEL-like 1 (chicken) 1.345471 0.035416 KRT7 keratin 7 1.345142 0.04343201 METTL11 #N/A 1.345064 0.02375531 A TRIM26 tripartite motif-containing 26 1.344982 0.04300975 KCNQ1 potassium voltage-gated channel, KQT-like 1.344976 0.04493967 subfamily, member 1 MTMR1 myotubularin related protein 12 1.34462 0.0317016 AMPH amphiphysin 1.344519 0.00793595 KCNK16 potassium channel, subfamily K, member 16 1.344179 0.01298541 CDKL2 cyclin-dependent kinase-like 2 (CDC2-related 1.343983 0.02627129 kinase) ACBD3 acyl-CoA binding domain containing 3 1.343979 0.0088417 FH fumarate hydratase 1.343761 0.01764835 LAPTM5 lysosomal protein transmembrane 5 1.343236 0.03239693 EIF3I eukaryotic translation initiation factor 3, subunit I 1.342791 0.03408126 ADAMTS ADAM metallopeptidase with thrombospondin 1.341872 0.01615138 6 type 1 motif, 6 PDCD6IP programmed cell death 6 interacting protein 1.341445 0.02712429 SCGN secretagogin, EF-hand calcium binding protein 1.341209 0.03145203 1/ 694375 16.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SHISA5 shisa homolog 5 (Xenopus laevis) 1.341148 0.04008168 COL4A1 collagen, type IV, alpha 1 1.340948 0.04402007 TMEM17 #N/A 1.340759 0.04828331 7 CTR9 Ctr9, Pafl/RNA polymerase II complex 1.340525 0.01367351 component, homolog (S. cerevisiae) WFDC6 #N/A 1.340339 0.03996958 ME3 malic enzyme 3, NADP(+)-dependent, 1.34006 0.04596134 mitochondrial FAM165B #N/A 1.339989 0.03564499 MOSPD3 motile sperm domain containing 3 1.339688 0.02672093 MED24 mediator complex subunit 24 1.338971 0.02234539 BCL3 B-cell CLL/lymphoma 3 1.338873 0.03515185 ZNF514 zinc finger protein 514 1.338774 0.03091846 Cllorf49 #N/A 1.338751 0.00600807 REX04 REX4, RNA exonuclease 4 homolog (S. 1.338363 0.02795145 cerevisiae) HNMT histamine N-methyltransferase 1.338353 0.01243209 ATPBD3 ATP binding domain 3 1.338268 0.03756416 XRCC1 X-ray repair complementing defective repair in 1.338228 0.02107989 Chinese hamster cells 1 ZKSCAN zinc finger with KRAB and SCAN domains 4 1.338143 0.01984388 4 GALC #N/A 1.337734 0.04874618 NBN nibrin 1.337492 0.01768605 C3orf31 chromosome 3 open reading frame 31 1.337435 0.03784451 WDR37 WD repeat domain 37 1.337261 0.04217673 DNASE1 deoxyribonuclease I-like 1 1.337125 0.0421296 LI REV3L REV3-like, catalytic subunit of DNA polymerase 1.337028 0.03337764 zeta (yeast) PRDM1 PR domain containing 1, with ZNF domain 1.336557 0.02794345 ASAP2 ArfGAP with SH3 domain, ankyrin repeat and PH 1.33651 0.04235299 domain 2 RNASE9 #N/A 1.336502 0.0239313 RAPGEF6 Rap guanine nucleotide exchange factor (GEF) 6 1.336214 0.03767711 MLLT3 myeloid/lymphoid or mixed-lineage leukemia 1.336207 0.0340955 (trithorax homolog, Drosophila); translocated to, 3 C20orf26 chromosome 20 open reading frame 26 1.33611 0.03564871 MUC20 mucin 20, cell surface associated 1.335759 0.03871754 ZNF271 zinc finger protein 271 1.335297 0.03003494 PTPRH protein tyrosine phosphatase, receptor type, H 1.335102 0.01 121867 CUX1 cut-like homeobox 1 1.334955 0.00914826 KCNA2 #N/A 1.334755 0.0481631 MY015B Myosin XVB pseudogene 1.334657 0.03628165 SLC7A60 solute carrier family 7, member 6 opposite strand 1.334654 0.04940768 S CFC1 cripto, FRL-1, cryptic family 1 1.33456 0.04856555 MLF1 myeloid leukemia factor 1 1.334552 0.00268692 TMEM14 transmembrane protein 143 1.334351 0.04652845 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 3 PLEKHN pleckstrin homology domain containing, family N 1.333813 0.01866753 1 member 1 MRPL2 Mitochondrial ribosomal protein L2 1.332717 0.03136737 CCDC28 coiled-coil domain containing 28A 1.332415 0.00567554 A Ά EPS 15 epidermal growth factor receptor pathway 1.332325 0.00937505 substrate 15 ATRNL1 attractin-like 1 1.33231 0.0185885 HERC4 hect domain and RLD 4 1.331943 0.04639538 COL4A6 collagen, type IV, alpha 6 1.331762 0.01428058 DR kinase insert domain receptor (a type III receptor 1.331501 0.01894919 tyrosine kinase) ASH1L ashl (absent, small, or homeotic)-like (Drosophila) 1.331452 0.03902654 L 1 low density lipoprotein receptor-related protein 1 1.331309 0.01612126 HIVEP1 human immunodeficiency virus type I enhancer 1.331277 0.0248194 binding protein 1 JMJD5 jumonji domain containing 5 1.33103 0.04885443 OR5M8 #N/A 1.331012 0.01957739 BEND4 #N/A 1.330633 0.0084728 CRLF3 cytokine receptor-like factor 3 1.330569 0.00382624 CD1E #N/A 1.330247 0.03326038 CABC1 Chaperone, ABC1 activity of bcl complex 1.330152 0.02028036 homolog (S. pombe) SFRS12IP SFRS12-interacting protein 1 1.330128 0.02220107 1 GPR1 10 G protein-coupled receptor 110 1.33003 0.03973178 ING4 inhibitor of growth family, member 4 1.3297 0.03081502 EPC2 enhancer of polycomb homolog 2 (Drosophila) 1.329573 0.00820874 FUCA2 fucosidase, alpha-L- 2, plasma 1.329563 0.00731294 STARD8 StAR-related lipid transfer (START) domain 1.32952 0.04361252 containing 8 NUFIP1 nuclear fragile X mental retardation protein 1.329454 0.04150613 interacting protein 1 TNR tenascin R (restrictin, janusin) 1.329092 0.04787231 ZNF33A zinc finger protein 33A 1.328976 0.03675665 TCN1 transcobalamin I (vitamin B12 binding protein, R 1.328809 0.04566794 binder family) RALY #N/A 1.32864 0.03824028 USP38 ubiquitin specific peptidase 3 1.328488 0.03761775 ACAD8 acyl-CoA dehydrogenase family, member 8 1.328208 0.00875427 OPLAH 5-oxoprolinase (ATP-hydrolysing) 1.328172 0.04351552 ISYNA1 #N/A 1.328122 0.02916504 RSI retinoschisin 1 1.328064 0.01333097 CLOCK clock homolog (mouse) 1.327919 0.02539796 ATF2 activating transcription factor 2 1.327908 0.00755993 SLC22A4 solute carrier family 22 (organic 1.327739 0.04834645 cation/ergothioneine transporter), member 4 BMP1 bone morphogenetic protein 1 1.32758 0.03343608 E2F1 #N/A 1.326853 0.01045809 DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value PGBD5 piggyBac transposable element derived 5 1.326672 0.03641358 KLK6 kallikrein-related peptidase 6 1.326072 0.0024961 LGTN ligatin 1.325635 0.01405736 ZNF174 zinc finger protein 174 1.325582 0.04896235 DAB2IP DAB2 interacting protein 1.325257 0.04430944 SYN1 synapsin l 1.324875 0.02786199 ERCC5 excision repair cross-complementing rodent repair 1.324623 0.03590136 deficiency, complementation group 5 SAMD 11 sterile alpha motif domain containing 11 1.324154 0.01895183 ZNF589 #N/A 1.324138 0.00889113 THBS2 thrombospondin 2 1.324 11 0.0 1874047 C2orf30 Chromosome 2 open reading frame 30 1.323884 0.04549174 HUS1 HUS1 checkpoint homolog (S. pombe) 1.323836 0.02917873 FMNL2 formin-like 2 1.323786 0.03096367 NCRNAO non-protein coding R A 95 1.323578 0.02733894 0095 PIH1D2 PIH1 domain containing 2 1.32339 0.01962435 HOMER2 homer homolog 2 (Drosophila) 1.32314 0.04783618 CLI T 1 clathrin interactor 1 1.322768 0.00691085 NTSR1 neurotensin receptor 1 (high affinity) 1.322725 0.0411674 FYN FYN oncogene related to SRC, FGR, YES 1.322618 0.04081056 RG9MTD RNA (guanine-9-) methyltransferase domain 1.322385 0.04548519 1 containing 1 EMR3 egf-like module containing, mucin-like, hormone 1.322343 0.03444567 receptor-like 3 C19orf57 chromosome 19 open reading frame 57 1.322321 0.02905814 C8orf71 chromosome 8 open reading frame 7 1 1.322233 0.01829096 SCP2 sterol carrier protein 2 1.322128 0.04065107 EPB41L3 Erythrocyte membrane protein band 4.1-like 3 1.321635 0.03609417 ZFPL1 #N/A 1.321634 0.00795096 MRPL3 mitochondrial ribosomal protein L3 1.321518 0.01629641 VIPR1 vasoactive intestinal peptide receptor 1 1.321242 0.0371231 CDH7 cadherin 7, type 2 1.320862 0.04295083 RPUSD2 #N/A 1.320642 0.02988753 CENPL centromere protein L 1.320641 0.01894421 SEC24C SEC24 family, member C (S. cerevisiae) 1.320333 0.0213207 CAP1 CAP, adenylate cyclase-associated protein 1 1.320275 0.04107121 (yeast) DNAJC5 #N/A 1.320198 0.04648958 G PDE7A phosphodiesterase 7A 1.320185 0.04566021 RHOBTB Rho-related BTB domain containing 2 1.31986 0.02694967 2 DPH3 DPH3, KTI1 1 homolog (S. cerevisiae) 1.319688 0.04772026 UBXN4 UBX domain protein 4 1.319595 0.04250153 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 1.31932 0.03201 1 2 RNASEL ribonuclease L (2',5'-oligoisoadenylate synthetase- 1.3192 0.02589713 dependent) ORC3L origin recognition complex, subunit 3-like (yeast) 1.318941 0.021 1371 SLFN11 #N/A 1.318215 0.02826722 / 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SH3RF1 SH3 domain containing ring finger 1 1.317529 0.00683851 WASF2 WAS protein family, member 2 1.316983 0.02117985 POGZ pogo transposable element with ZNF domain 1.316888 0.03835929 AKAP13 A kinase (PRKA) anchor protein 13 1.316226 0.0189134 PPP1R1B Protein phosphatase 1, regulatory (inhibitor) 1.316203 0.02374975 subunit B (dopamine and cAMP regulated phosphoprotein, DARPP-32) TSKS testis-specific serine kinase substrate 1.315893 0.00713658 KIR2DL2 killer cell immunoglobulin-like receptor, two 1.315851 0.0 1475652 domains, long cytoplasmic tail, 2 FAM109A family with sequence similarity 109, member A 1.315757 0.02257493 MAGEL2 #N/A 1.315658 0.04378946 PTH1R parathyroid hormone 1 receptor 1.315632 0.0486571 MYH2 myosin, heavy chain 2, skeletal muscle, adult 1.315621 0.00327681 COMMD1 copper metabolism (Murrl) domain containing 1 1.315589 0.04072324 PIWIL4 Piwi-like 4 (Drosophila) 1.315555 0.00434309 RCAN1 regulator of calcineurin 1 1.315489 0.02339676 ZEB1 zinc finger E-box binding homeobox 1 1.314865 0.04632938 MAP3K13 mitogen-activated protein kinase kinase kinase 13 1.314721 0.02698734 HDAC5 histone deacetylase 5 1.313934 0.0481495 SEMA3C sema domain, immunoglobulin domain (Ig), short 1.3 3924 0.0488503 1 basic domain, secreted, (semaphorin) 3C SMAD6 SMAD family member 6 1.313915 0.04895342 PFT 1 PFTAIRE protein kinase 1 1.313884 0.01269846 SERPINA Serpin peptidase inhibitor, clade A (alpha- 1 1.313754 0.00679302 9 antiproteinase, antitrypsin), member 9 ACATI acetyl-CoA acetyltransferase 1 1.313644 0.04753139 CAPN7 Calpain 7 1.313621 0.03062464 HPD #N/A 1.313449 0.04917888 NUP155 nucleoporin 155kDa 1.313273 0.0391 177 MMP10 #N/A 1.313052 0.00879522 ECM2 extracellular matrix protein 2, female organ and 1.3 1297 0.04898875 adipocyte specific ACTBL3 #N/A 1.31287 0.00406906 HLA- #N/A 1.312829 0.04824824 DRB5 KHSRP KH-type splicing regulatory protein 1.312595 0.03596163 APBB3 amyloid beta (A4) precursor protein-binding, 1.3 12555 0.03722342 family B, member 3 UGT2B28 UDP glucuronosyltransferase 2 family, 1.312459 0.04065599 polypeptide B28 WFDC12 #N/A 1.31236 0.04720783 IFT8 1 intraflagellar transport 81 homolog 1.3 1208 1 0.0241 023 (Chlamydomonas) ARPC1B actin related protein 2/3 complex, subunit IB, 1.31 1651 0.02753439 41kDa MICAL2 microtubule associated monoxygenase, calponin 1.31 1573 0.01533516 and LIM domain containing 2 ZNF193 zinc finger protein 193 1.31 1509 0.02200133 KCNAB1 potassium voltage-gated channel, shaker-related .3 1142 0.03 159023 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value subfamily, beta member 1 GRINA glutamate receptor, ionotropic, N-methyl D- 1.31 1403 0.03669983 aspartate-associated protein 1 (glutamate binding) ANGPTL angiopoietin-like 6 1.31 1251 0.04023643 6 CCDC125 coiled-coil domain containing 125 1.31 1077 0.04961275 HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 1.310916 0.01609754 (soluble) NUS1 nuclear undecaprenyl pyrophosphate synthase 1 1.31088 0.03638989 homolog (S. cerevisiae) ANXA8 annexin A8 1.310877 0.04901674 C8orf55 chromosome 8 open reading frame 55 1.310792 0.04199884 CREG1 cellular repressor of ElA-stimulated genes 1 1.310534 0.02867724 RCC2 regulator of chromosome condensation 2 1.309952 0.02529485 MYH13 myosin, heavy chain 13, skeletal muscle 1.309813 0.00229448 ARID 1A AT rich interactive domain 1A (SWI-like) 1.309753 0.0241035 ST6GAL ST6 (alpha-N-acetyl-neuraminyl-2,3 -beta- 1.309637 0.00775862 NAC1 galactosyl- 1,3)-N-acetylgalactosaminide alpha- 2,6-sialyltransferase 1 SCGB1C1 secretoglobin, family 1C, member 1 1.30957 0.01019826 C l lorf79 Chromosome 11 open reading frame 79 1.309097 0.02724393 GSTCD glutathione S-transferase, C-terminal domain 1.308976 0.00023955 containing PIK3CB phosphoinositide-3-kinase, catalytic, beta 1.308634 0.03742953 polypeptide EPRS glutamyl-prolyl-tRNA synthetase 1.308599 0.02361163 SUPT5H suppressor of Ty 5 homolog (S. cerevisiae) 1.307863 0.01749818 IL18RAP interleukin 18 receptor accessory protein 1.307668 0.0227035 SLC30A3 solute carrier family 30 (zinc transporter), member 1.307468 0.01544482 3 CDC42EP #N/A 1.306756 0.04378984 3 P2RX3 purinergic receptor P2X, ligand-gated ion channel, 1.306563 0.03962583 3 DPF1 D4, zinc and double PHD fingers family 1 1.306337 0.01809137 WT1 Wilms tumor 1 1.306117 0.03913065 C7orf52 chromosome 7 open reading frame 52 1.305718 0.00211672 ZNF622 zinc finger protein 622 1.305364 0.03391459 C4orf33 chromosome 4 open reading frame 3 1.305078 0.03778524 CLCC1 chloride channel CLIC-like 1 1.30507 0.03679493 ATP1B2 ATPase, Na+/ + transporting, beta 2 polypeptide 1.305069 0.01874 MANEAL mannosidase, endo-alpha-like 1.304964 0.03096874 COL7A1 collagen, type VII, alpha 1 1.3043 0.04893659 ZHX3 zinc fingers and homeoboxes 3 1.304281 0.00510183 RASGRF1 Ras protein-specific guanine nucleotide-releasing 1.304227 0.02912166 factor 1 ZNF215 zinc finger protein 215 1.303954 0.01264929 ZC3H11A zinc finger CCCH-type containing 11A 1.303881 0.04908546 NEIL3 nei endonuclease VHI-like 3 (E. coli) 1.303447 0.04056936 PRODH proline dehydrogenase (oxidase) 1 1.303404 0.04779837 DBl/69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value MED25 mediator complex subunit 25 1.303334 0.03529458 CYP27A1 #N/A 1.303212 0.03372699 GFRAL #N/A 1.303147 0.00927841 CLK2 CDC-like kinase 2 1.302684 0.02715932 CDC2L1 #N/A 1.302623 0.00493949 ONECUT one cut homeobox 1 1.30261 0.02150041 1 DARS aspartyl-tRNA synthetase 1.302588 0.03877241 CPNE4 #N/A 1.302533 0.03382635 RELT RELT tumor necrosis factor receptor 1.302513 0.00307975 POU4F1 POU class 4 homeobox 1 1.302303 0.03003303 Pll 26 serine protease 1.302277 0.01666558 AN S6 #N/A 1.30191 0.01732197 ARMET Arginine-rich, mutated in early stage tumors 1.301554 0.02325872 EXOSC9 exosome component 9 1.301209 0.02001717 GOLGA1 golgin A l 1.301101 0.00409553 MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1.301052 0.00303927 1 (E. coli) MAML3 mastermind-like 3 (Drosophila) 1.300927 0.04496825 DDX21 #N/A 1.30083 0.02404695 GPR50 G protein-coupled receptor 50 1.300636 0.03631905 TGM4 transglutaminase 4 (prostate) 1.300431 0.04895508 POLR3F polymerase (RNA) III (DNA directed) polypeptide 1.299365 0.03626355 F, 39 kDa TMEM12 transmembrane protein 125 1.29855 0.02820931 J DMRTC1 DMRT-like family CI 1.298315 0.01042075 PRKAB1 protein kinase, AMP-activated, beta 1 non- 1.298097 0.04325755 catalytic subunit DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9 1.297972 0.02876581 KRT222P Keratin 222 pseudogene 1.297831 0.03679215 YIF1A Yipl interacting factor homolog A (S. cerevisiae) 1.297603 0.03754831 TCF12 transcription factor 12 1.297588 0.0231 1339 ALPPL2 #N/A 1.297346 0.0301 1951 SPRY3 sprouty homolog 3 (Drosophila) 1.297167 0.04437122 MITD1 MIT, microtubule interacting and transport, 1.29714 0.03856481 domain containing 1 ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of 1.296809 0.03941384 VLA-2 receptor) CAP2 CAP, adenylate cyclase-associated protein, 2 1.296647 0.00235809 (yeast) ZBTB9 zinc finger and BTB domain containing 9 1.296604 0.02182821 LIN7B lin-7 homolog B (C. elegans) 1.296549 0.01491215 PRR5 proline rich 5 (renal) 1.29601 0.03296957 KCNQ3 potassium voltage-gated channel, KQT-like 1.295465 0.00988049 subfamily, member 3 GATAD2 GATA zinc finger domain containing 2B 1.295344 0.0051653 r SLC12A3 solute carrier family 12 (sodium/chloride 1.295226 0.0361613 transporters), member 3 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value DUS3L dihydrouridine synthase 3-like (S. cerevisiae) 1.294954 0.03184389 GPR1 3 G protein-coupled receptor 1 1.294818 0.0368055 NBPF4 neuroblastoma breakpoint family, member 4 1.294176 0.03458487 GNAS GNAS complex locus 1.2941 13 0.02526419 HNF4A hepatocyte nuclear factor 4, alpha 1.293896 0.02932833 RA 1 RAD1 homolog (S. pombe) 1.293558 0.0171556 UQCRQ ubiquinol-cytochrome c reductase, complex III 1.29346 0.04854268 subunit VII, 9.5kDa CALCRL #N/A 1.293072 0.02451256 RPP14 ribonuclease P/MRP 14kDa subunit 1.29301 0.04069763 COL12A1 collagen, type XII, alpha 1 1.29279 0.04414952 LY75 lymphocyte antigen 75 1.292702 0.0057195 PPFIA1 protein tyrosine phosphatase, receptor type, f 1.292575 0.03195209 polypeptide (PTPRF), interacting protein (liprin), alpha 1 WDR23 WD repeat domain 23 1.292564 0.02314096 MY03B myosin IIIB 1.292237 0.03247619 LRCH2 leucine-rich repeats and calponin homology (CH) 1.292236 0.0130786 domain containing 2 ZNF578 zinc finger protein 578 1.292192 0.03081413 PDK4 pyruvate dehydrogenase kinase, isozyme 4 1.292167 0.02978736 BTN3A2 butyrophilin, subfamily 3, member A2 1.2921 0.04600277 ZNF570 zinc finger protein 570 1.291793 0.04084999 ASTN1 astrotactin 1 1.291557 0.0244782 TMEM10 transmembrane protein 101 1.291523 0.01355169 1 LEAP2 #N/A 1.290898 0.01576343 FAM46A family with sequence similarity 46, member A 1.290802 0.01962303 TRIP4 Thyroid hormone receptor interactor 4 1.290743 0.04337559 LOC4006 #N/A 1.289945 0.01369745 96 ABL1 c-abl oncogene 1, receptor tyrosine kinase 1.289406 0.04543309 COL2A1 collagen, type II, alpha 1 1.289223 0.03761942 TBC1D1 TBCl (tre-2/USP6, BUB2, cdcl6) domain family, 1.289144 0.01925313 member 1 MY07A myosin VIIA 1.288321 0.0491 1618 SNHG3 small nucleolar RNA host gene 3 (non-protein 1.288272 0.00957217 coding) S1AE sialic acid acetylesterase 1.288003 0.04485108 OR1Q1 #N/A 1.287798 0.00170856 DIP2B DIP2 disco-interacting protein 2 homolog B 1.287687 0.0218845 (Drosophila) ARHGEF Rho guanine nucleotide exchange factor (GEF) 7 1.287534 0.0405397 7 LIPF lipase, gastric 1.287407 0.02793804 F5 coagulation factor V (proaccelerin, labile factor) 1.287381 0.01953173 OR1S1 Olfactory receptor, family 1, subfamily S, member 1.287 109 0.00690034 1 ATF5 #N/A 1.286814 0.0497241 1 RALGPS2 Ral GEF with PH domain and SH3 binding motif 1.286257 0.04061583 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value 2 BCAN brevican 1.286146 0.03577875 Fll coagulation factor XI 1.285686 0.02838542 GREM2 #N/A 1.285532 0.04360017 TORIAIP torsin A interacting protein 2 1.285517 0.02358602 2 GPS1 #N/A 1.285464 0.04388261 ABCA6 ATP-binding cassette, sub-family A (ABC1), 1.285056 0.03 126701 member 6 HOXC12 #N/A 1.285033 0.03233783 ADPRHL ADP-ribosylhydrolase like 2 1.285009 0.04195797 2 FXYD1 #N/A 1.284826 0.04189004 CLEC5A #N/A 1.284664 0.03995698 HDGF hepatoma-derived growth factor 1.284638 0.04400985 SPOPL speckle-type POZ protein-like 1.284296 0.03378694 C17orf73 chromosome 7 open reading frame 73 1.284227 0.02929441 EBF1 #N/A 1.284106 0.04508284 DAG1 dystroglycan 1 (dystrophin-associated 1.284098 0.00984698 glycoprotein 1) PXN paxillin 1.283966 0.048801 14 ARHGAP R o GTPase activating protein 0 .283 734 0.02955473 10 B3GALT6 UDP-Gal:betaGal beta 1,3-galactosyltransferase 1.283705 0.01387262 polypeptide 6 MIDI #N/A 1.283608 0.03838221 FLJ26056 #N/A 1.283583 0.03857654 C14orfl59 chromosome 14 open reading frame 159 1.28356 0.043791 16 ATAD3B ATPase family, AAA domain containing 3B 1.283442 0.0479323 IQCA1 IQ motif containing with AAA domain 1 1.282184 0.00914257 RXFP1 relaxin/insulin-like family peptide receptor 1 1.282122 0.00278521 CRYGB crystallin, gamma B 1.282066 0.02889521 ADCY10 adenylate cyclase 10 (soluble) 1.28206 0.04725498 NSUN3 #N/A 1.281746 0.04989998 DUOX2 dual oxidase 2 1.281683 0.04227892 KNDC1 kinase non-catalytic C-lobe domain (KIND) 1.280672 0.03136853 containing 1 STX1B syntaxin I 1.280564 0.01411697 SLC4A8 solute carrier family 4, sodium bicarbonate 1.280486 0.04023173 cotransporter, member 8 RPL7L1 ribosomal protein L7-like 1 1.280321 0.0449192 DMXL2 Dmx-like 2 1.280287 0.04149996 GPR81 G protein-coupled receptor 8 1 1.280119 0.03239705 EIF4E3 eukaryotic translation initiation factor 4E family 1.279238 0.02679712 member 3 PRKRA protein kinase, interferon-inducible double 1.278927 0.03584581 stranded RNA dependent activator TEX11 testis expressed 11 1.278877 0.03709168 HSPA9 heat shock 70kDa protein 9 (mortalin) 1.278665 0.01554267 PAX5 paired box 5 1.278361 0.01289398 D / 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value CYP4X1 cytochrome P450, family 4, subfamily X, 1.27801 0.03550355 polypeptide 1 DNAH7 dynein, axonemal, heavy chain 7 1.277659 0.04289445 MAPK8IP mitogen-activated protein kinase 8 interacting 1.277633 0.03321973 3 protein 3 KLHDC9 kelch domain containing 9 1.277612 0.04814524 PCDHB17 #N/A 1.277596 0.03612841 FBX09 F-box protein 9 1.276761 0.02422462 APCDD1 #N/A 1.27674 0.03973463 MBTPS membrane-bound transcription factor peptidase, 1.27672 0.04423689 site 1 GTF2I general transcription factor i 1.276479 0.03942891 HSPC 159 galectin-related protein 1.276374 0.0439434 MAP3K6 mitogen-activated protein kinase kinase kinase 6 1.275563 0.01955517 MRPS5 mitochondrial ribosomal protein S5 1.275511 0.01551 189 CASP3 caspase 3, apoptosis-related cysteine peptidase 1.275471 0.00672259 PKN2 protein kinase N2 1.275239 0.02515919 PDE6D phosphodiesterase 6D, cGMP-specific, rod, delta 1.275132 0.01303783 RNF 144B ring finger protein 144B 1.275124 0.04620057 FAM138D #N/A 1.275058 0.03045217 C12orf52 chromosome 1 open reading frame 52 1.274935 0.04444509 MTA3 Metastasis associated 1 family, member 3 1.274622 0.03563214 MADD MAP-kinase activating death domain 1.274143 0.04855802 TRMT6 1 t NA methyltransferase 6 homoiog B (S. 1.273568 0.02526202 B cerevisiae) ZNF14 zinc finger protein 1.272835 0.03423005 FAM124A family with sequence similarity 1 4A 1.272775 0.04168444 DIXDCl #N/A 1.2725 0.04072744 FCRL5 Fc receptor-like 5 1.272331 0.03206552 COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen) 1.272118 0.02337824 SLC1 1A2 solute carrier family 11 (proton-coupled divalent 1.27202 0.01701597 metal ion transporters), member 2 OR10G4 Olfactory receptor, family 10, subfamily G, 1.271988 0.02930133 member 4 NPR2 natriuretic peptide receptor B/guanylate cyclase B 1.271875 0.03567998 (atrionatriuretic peptide receptor B) DAZ1 deleted in azoospermia 1 1.271743 0.01264477 ATP2B3 ATPase, Ca++ transporting, plasma membrane 3 1.271474 0.0447933 PI15 peptidase inhibitor 15 1.271393 0.04151015 NSMCE2 non-SMC element 2, MMS21 homoiog (S. 1.271363 0.02515466 cerevisiae) HYDIN hydrocephalus inducing homoiog (mouse) 1.27123 0.03905987 C19orf5 chromosome 19 open reading frame 5 1.271 156 0.0284778 STK3 1 serine/threonine kinase 31 1.271058 0.02681916 COPB2 coatomer protein complex, subunit beta 2 (beta 1.270956 0.02084552 prime) SLC19A2 solute carrier family 1 (thiamine transporter), 1.270824 0.00397826 member 2 ZFP28 zinc finger protein 28 homoiog (mouse) 1.270796 0.03986652 IFNA17 #N/A 1.27064 0.00548264 DB1/ 694 3 7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value UAP1L1 UDP-N-acteylglucosamine pyrophosphorylase 1- 1.270479 0.0296152 like 1 GDA #N/A 1.27041 1 0.03882797 PRKAB2 protein kinase, AMP-activated, beta 2 non- 1.270082 0.03231 157 catalytic subunit ZNF425 Zinc finger protein 425 1.270009 0.04598816 WWC1 WW and C2 domain containing 1 1.269983 0.04551941 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), 1.269778 0.02854381 member 1 PDCL2 phosducin-like 2 1.269367 0.00061538 C14orf39 chromosome 14 open reading frame 39 1.269251 0.01571564 OR5V1 #N/A 1.268983 0.03792536 YARS tyrosyl-tRNA synthetase 1.26819 0.01419457 RIBC2 #N/A 1.268036 0.02692288 GPR89A G protein-coupled receptor 89A 1.267631 0.02533276 PARVA parvin, alpha 1.267495 0.02553094 LYPD6 LY6/PLAUR domain containing 6 1.267092 0.04639769 CASQ2 #N/A 1.267042 0.00722503 ARFIP1 ADP-ribosylation factor interacting protein 1 1.266696 0.04164397 NUP88 nucleoporin 88kDa 1.266061 0.04223257 PLXNA4 Plexin A4 1.26585 0.02073357 DNAH8 dynein, axonemal, heavy chain 8 1.265201 0.00013086 BUB1 budding uninhibited by benzimidazoles 1 homolog 1.26498 0.04131477 (yeast) HSPA12B heat shock 70kD protein 12B 1.264936 0.03344558 AN RD 1 ankyrin repeat domain 12 1.26444 0.03384275 z AP2A1 adaptor-related protein complex 2, alpha 1 subunit 1.26436 0.04642281 ATIC 5-aminoimidazole-4-carboxamide ribonucleotide 1.264237 0.03857019 formyltransferase/IMP cyclohydrolase MYOCD myocardin 1.264143 0.011 17924 TRIM36 tripartite motif-containing 36 1.263855 0.04894895 KIAA0 KIAA0195 1.263548 0.04435687 J MRPS25 Mitochondrial ribosomal protein S25 1.26347 0.01791241 PCDHGC protocadherin gamma subfamily C, 5 1.263433 0.04118921

PRPF39 PRP39 pre-mRNA processing factor 39 homolog 1.263236 0.03313913 (S. cerevisiae) IP09 importin 9 1.262536 0.03239699 BCAS3 Breast carcinoma amplified sequence 3 1.262477 0.01277402 METTL4 #N/A 1.262252 0.01031767 MAP3K11 mitogen-activated protein kinase kinase kinase 11 1.262091 0.02976909 FAM92A1 family with sequence similarity 92, member A l 1.262032 0.04147755 ZNF781 zinc finger protein 781 1.261777 0.00937657 PPM IF protein phosphatase, Mg2+/Mn2+ dependent, IF 1.261501 0.00705184 CCDC52 coiled-coil domain containing 52 1.261425 0.01610132 PC pyruvate carboxylase 1.261405 0.00486587 GGTA1 glycoprotein, alpha-galactosyltransferase 1 1.261257 0.00876746 pseudogene DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value RHBDD2 rhomboid domain containing 2 1.260801 0.00848564 VSTM1 #N/A 1.26072 0.04402841 TNNI3K TN I3 interacting kinase 1.2606 0.04011763 GLIS3 GLIS family zinc finger 3 1.260323 0.01659638 ZNF613 zinc finger protein 613 1.258929 0.00352566 CXorf40A chromosome X open reading frame 40A 1.258447 0.01336367 KIF21A kinesin family member 2 1A 1.257661 0.01839864 RILP Rab interacting lysosomal protein 1.257525 0.0052284 TRIM58 tripartite motif-containing 58 1.257469 0.04056475 PTPRA protein tyrosine phosphatase, receptor type, A 1.257443 0.02131531 TAGAP T-cell activation GTPase activating protein 1.256328 0.01003539 MCM3 minichromosome maintenance complex 1.256221 0.01483353 component 3 GIPC2 GIPC PDZ domain containing family, member 2 1.255826 0.03658988 POLR3E polymerase (RNA) III (DNA directed) polypeptide 1.2556 0.0032588 E (80kD) PPP R 0 protein phosphatase 1, regulatory (inhibitor) 1.255596 0.04773474 subunit 10 SNX27 sorting nexin family member 27 1.255409 0.02661206 ABCF2 ATP-binding cassette, sub-family F (GCN20), 1.254928 0.00078914 member 2 NT5DC1 5'-nucleotidase domain containing 1 1.254258 0.03833736 ZFX #N/A 1.254057 0.02842691 TNKS1BP tankyrase 1 binding protein 1, 182kDa 1.254051 0.0267223 1 CP1 10 CP1 10 protein 1.253971 0.02752672 PASD1 PAS domain containing 1 1.253623 0.00725862 PQLC2 PQ loop repeat containing 2 1.253527 0.0481956 TPCN1 two pore segment channel 1 1.253329 0.02771144 POM121 POM1 2 1 membrane glycoprotein (rat) 1.25332 0.04289457 STRBP spermatid perinuclear RNA binding protein 1.253091 0.02912347 COASY CoA synthase 1.252781 0.04184411 RAF1 v-raf-1 murine leukemia viral oncogene homolog 1.252769 0.02889318 1 CPSF3 cleavage and polyadenylation specific factor 3, .252728 0. 347429 73kDa PDGFRB platelet-derived growth factor receptor, beta 1.2526 0.01825528 polypeptide OR11L1 Olfactory receptor, family 11, subfamily L, 1.252538 0.03151985 member 1 MAP2K3 mitogen-activated protein kinase kinase 3 1.252382 0.01292775 MAGEC2 melanoma antigen family C, 2 1.251806 0.04643824 HRASLS HRAS-like suppressor 1.251591 0.01555165 HNF4G #N/A 1.251585 0.04917062 TD02 tryptophan 2,3-dioxygenase 1.251091 0.01531997 TFG TRK-fused gene 1.251084 0.02019895 MAT2B methionine adenosyltransferase II, beta 1.250962 0.00601561 ERAP2 endoplasmic reticulum aminopeptidase 2 1.250556 0.02769817 LIMCH1 LIM and calponin homology domains 1 1.24951 0.03223645 COL4A4 collagen, type IV, alpha 4 1.249353 0.03545571 DBl/ 69437516. 1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value FAM86C family with sequence similarity 86, member C 1.249117 0.03879044 ASGR2 asialoglycoprotein receptor 2 1.249028 0.04655806 TOM1 target of mybl (chicken) 1.248495 0.01800626 DAB2 disabled homolog 2, mitogen-responsive 1.248421 0.03947221 phosphoprotein (Drosophila) EHBP1 EH domain binding protein 1 1.248177 0.03923267 COPS4 COP9 constitutive photomorphogenic homolog 1.247876 0.04658872 subunit 4 (Arabidopsis) MMP3 #N/A 1.246785 0.01655688 TANK TRAF family member-associated NFKB activator 1.24674 0.02488358 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.246722 0.01259013 ATF4 activating transcription factor 4 (tax-responsive 1.246548 0.00900501 enhancer element B67) ADAMTS ADAMTS-like 3 1.246259 0.02218159 L3 RNASEH ribonuclease H2, subunit B 1.245775 0.04827555 2B KIAA126 KIAA1267 1.245732 0.04533407 7 MIOS missing oocyte, meiosis regulator, homolog 1.245244 0.03115889 (Drosophila) FAM84B family with sequence similarity 84, member B 1.245212 0.03957666 GNPTAB N-acetylglucosamine- 1-phosphate transferase, 1.244249 0.02637465 alpha and beta subunits C7orf28A chromosome 7 open reading frame 28A 1.244241 0.01 136235 FGL1 fibrinogen-like 1 1.243607 0.03424585 FDPS farnesyl diphosphate synthase (farnesyl 1.243357 0.01230338 pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase) HCCS #N/A 1.243197 0.04454228 EIF4EBP1 eukaryotic translation initiation factor 4E binding 1.242901 0.03329666 protein 1 GLMN glomulin, FKBP associated protein 1.242806 0.01074317 SLC36A3 solute carrier family 36 (proton/amino acid 1.242714 0.03471447 symporter), member 3 HR Hairless homolog (mouse) 1.242273 0.01561571 CACNA1 #N/A 1.24211 0.01850723 F FLJ38723 hypothetical FLJ3 8723 1.241923 0.01852625 ZNF143 zinc finger protein 143 1.241752 0.03860238 SU 12 suppressor of zeste 2 homolog (Drosophila) 1.241237 0.04277373 PON3 paraoxonase 3 1.2403 0.01155334 C14orf21 #N/A 1.2401 19 0.03267246 HTR3B #N/A 1.239835 0.03170828 FBXL4 F-box and leucine-rich repeat protein 4 1.239726 0.03680803 MIB1 mindbomb homolog 1 (Drosophila) 1.239452 0.03698461 ZHX2 zinc fingers and homeoboxes 2 1.239388 0.00501939 NDST4 N-deacetylase/N-sulfotransferase (heparan 1.239191 0.02903312 glucosaminyl) 4 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value VWA1 #N/A 1.239135 0.01 162727 PRKAR1 protein kinase, cAMP-dependent, regulatory, type .23 851 0.003 12229 A I, alpha (tissue specific extinguisher 1) NCOA7 nuclear receptor coactivator 7 1.23 7865 0.00 128132 GBP6 guanylate binding protein family, member 6 1.237788 0.03008652 CALCOC calcium binding and coiled-coil domain 1 1.237698 0.04981056 0 1 AKNA AT-hook transcription factor 1.237234 0.03152078 AN02 anoctamin 2 1.236902 0.04959632 COL17A1 collagen, type XVII, alpha 1 1.236684 0.0447795 GLT1D1 #N/A 1.236359 0.03506938 C7orf53 #N/A 1.235726 0.04031539 PANK2 Pantothenate kinase 2 (Hallervorden-Spatz .235 141 0.03673737 syndrome) RPSAP52 ribosomal protein SA pseudogene 52 1.234438 0.02712198 LCE4A #N/A 1.234144 0.01137053 TAF7 TAF7 RNA polymerase II, TATA box binding 1.233448 0.04085823 protein (TBP)-associated factor, 55kDa KIF5C kinesin family member 5C 1.232486 0.03748713 WNT2 wingless-type MMTV integration site family 1.23233 1 0.01 137624 member 2 NCKAP1 NCK-associated protein 1-like 1.231943 0.04050152 L LOC4420 hypothetical LOC442028 1.231005 0.02574421 28 MUC21 mucin 2 1, cell surface associated 1.230888 0.00636689 ZNF280B zinc finger protein 280B 1.2293 1 0.04300624 RU DC3 RUN domain containing 3A 1.229173 0.01050238 A DHRS7 dehydrogenase/reductase (SDR family) member 7 1.228972 0.02059347 CEP 120 centrosomal protein 120kDa 1.228739 0.04280283 ZNF740 zinc finger protein 740 1.228 139 0.0448329 BXDC5 Brix domain containing 5 1.228102 0.02902991 APITD1 apoptosis-inducing, TAF9-like domain 1 1.227749 0.0267092 IKBKB inhibitor of kappa light polypeptide gene enhancer 1.22676 0.02 3 in B-cells, kinase beta LSP1 lymphocyte-specific protein 1 1.226601 0.02056225 ACACB acetyl-CoA carboxylase beta 1.226541 0.04957428 PARL presenilin associated, rhomboid-like 1.226446 0.0367682 GJA5 gap junction protein, alpha 5, 40kDa 1.226313 0.03889361 L3MBTL l(3)mbt-like (Drosophila) 1.225892 0.01802015 WDSOF1 WD repeats and SOF1 domain containing 1.225379 0.01660816 NFKBIB nuclear factor of kappa light polypeptide gene 1.224 185 0.03315169 enhancer in B-cells inhibitor, beta IFRD1 interferon-related developmental regulator 1 1.223621 0.0461768 RBMY1A RNA binding motif protein, Y-linked, family 1, 1.223569 0.04076852 1 member Al GPRIN3 #N/A 1.223357 0.04888478 LOCIOOI hypothetical protein LOC100129608 1.223183 0.01528767 29608 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value ARID IB AT rich interactive domain IB (SWIl-like) 1.223178 0.02072647 SPOCK3 sparc/osteonectin, cwcv and kazal-like domains 1.222704 0.02605689 proteoglycan (testican) 3 RNASEH ribonuclease H I 1.22204 0.02031 113 1 BHLHE22 basic heli -loop-helix family, member e22 1.221705 0.04813503 PTK6 PTK6 protein tyrosine kinase 6 1.221542 0.02077182 CRISPl cysteine-rich secretory protein 1 1.221404 0.04691411 PSMD3 proteasome (prosome, macropain) 26S subunit, 1.220652 0.04587661 non-ATPase, 3 IRS2 insulin receptor substrate 2 1.219897 0.01398234 PTGER4 #N/A 1.21928 0.00509381 USP9Y ubiquitin specific peptidase 9, Y-linked 1.219224 0.01601733 ACADVL acyl-CoA dehydrogenase, very long chain 1.218665 0.03752542 CHL1 cell adhesion molecule with homology to L ICAM 1.218548 0.0364314 (close homolog of LI) RIMS2 regulating synaptic membrane exocytosis 2 1.218523 0.00582967 ADAM22 ADAM metallopeptidase domain 22 1.218147 0.04977676 PMS1 PMS1 postmeiotic segregation increased 1 (S. 1.217981 0.03860087 cerevisiae) KIF1A kinesin family member 1A 1.21752 0.00196066 X R6 XK, Kell blood group complex subunit-related 1.21749 0.04322222 family, member 6 USP7 ubiquitin specific peptidase 7 (herpes virus- 1.2173 0.03971564 associated) TRHDE #N/A 1.216856 0.01790775 GAS2L2 growth arrest-specific 2 like 2 1.216707 0.00746077 SCAND3 SCAN domain containing 3 1.216047 0.04952198 MOCS2 molybdenum cofactor synthesis 2 1.215847 0.04158688 PYGB phosphorylase, glycogen; brain 1.214217 0.04721694 CDC26 Cell division cycle 26 homolog (S. cerevisiae) 1.214154 0.04346382 PLSCR1 phospholipid scramblase 1 1.213882 0.04871947 IMPG1 interphotoreceptor matrix proteoglycan 1 1.212979 0.02801435 MMP8 matrix metallopeptidase 8 (neutrophil collagenase) 1.212836 0.01042643 SMARCA SWI/SNF related, matrix associated, actin 1.212641 0.01091184 5 dependent regulator of chromatin, subfamily a, member 5 FAM182A #N/A 1.212618 0.03154097 NIN ninein (GSK3B interacting protein) 1.212281 0.03559446 NTRK3 neurotrophic tyrosine kinase, receptor, type 3 1.211585 0.03948024 PPA2 pyrophosphatase (inorganic) 2 1.21 132 0.04234664 RG9MTD RNA (guanine-9-) methyltransferase domain 1.210992 0.00622261 3 containing 3 ALDH16 aldehyde dehydrogenase 1 family, member A l 1.210101 0.03869864 A l IL9R interleukin 9 receptor 1.210046 0.04769692 NSMCE4 non-SMC element 4 homolog A (S. cerevisiae) 1.2097 17 0.036 10428 A NEXN nexilin (F actin binding protein) 1.209156 0.01265075 SOX30 SRY (sex determining region Y)-box 30 1.208577 0.03233023 DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value SYN2 synapsin ll 1.20705 0.02188363 FAM136A #N/A 1.206366 0.02512492 UBAP2L ubiquitin associated protein 2-like 1.205878 0.04256504 TAGLN3 transgelin 3 1.204673 0.01504545 KCNH2 potassium voltage-gated channel, subfamily H 1.204637 0.047328 18 (eag-related), member 2 DE ND4 DENN/MADD domain containing 4A 1.204522 0.03533718 A RBM38 RNA binding motif protein 38 1.204225 0.02843861 C14orf53 #N/A 1.203751 0.04928678 DDX1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 1 1.203 82 0.04887201 METTL8 methyltransferase like 8 1.203 141 0.042963 81 RABEP1 rabaptin, RAB GTPase binding effector protein 1 1.202797 0.0453 199 CYLC2 cylicin, basic protein of sperm head cytoskeleton 2 1.202599 0.03060352 CLCA4 chloride channel accessory 4 1.201348 0.03271975 SLC22A2 solute carrier family 22 (organic cation 1.200369 0.046401 89 transporter), member 2 CREB1 cAMP responsive element binding protein 1 1.199173 0.02092548 CCDC74 coiled-coil domain containing 74A 1.197072 0.03380953 A RPL35 ribosomal protein L35 1.196344 0.03583088 C16orf89 chromosome 1 open reading frame 89 1.195652 0.03712854 GYLTL1 glycosyltransferase-like IB 1.195435 0.01664133 B CRTAP cartilage associated protein 1.194501 0.01415943 AR T aryl hydrocarbon receptor nuclear translocator 1.194489 0.037 11559 PPP1CB protein phosphatase 1, catalytic subunit, beta 1. 9403 1 0.01 004224 isozyme ACVR2A activin A receptor, type IIA 1.194004 0.04361939 CYP11B2 cytochrome P450, family 11, subfamily B, 1.193589 0.04786336 polypeptide 2 C5orfl3 chromosome 5 open reading frame 13 1.193585 0.04570836 C3orf57 chromosome 3 open reading frame 57 1.192686 0.04563884 PLD5 #N/A 1.192032 0.01557073 DBI diazepam binding inhibitor (GABA receptor 1.191704 0.033454 18 modulator, acyl-CoA binding protein) KLF2 #N/A 1.19143 0.02001404 RPL13AP #N/A 1.190779 0.03599393 5 C17orf80 chromosome 17 open reading frame 80 1.18979 0.02904241 THEM4 thioesterase superfamily member 4 1.189005 0.04797765 DNAJC12 #N/A 1.186992 0.03956968 KIAA019 KIAA0196 1.185084 0.01295962 6 MTERFD #N/A 1.184715 0.02707179 1 NMD3 NMD3 homolog (S. cerevisiae) 1.184712 0.03234417 RNF220 ring finger protein 220 1.182256 0.01 184286 PRKAR2 protein kinase, cAMP-dependent, regulatory, type 1.182192 0.02527208 A II, alpha D V 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value MYOZ3 myozenin 3 1.181691 0.01236801 CHCHD3 coiled-coil-helix-coiled-coil-helix domain 1.181329 0.02752 containing 3 GLI1 GLI family zinc finger 1 1.1812 0.04533189 RHEB Ras homolog enriched in brain 1.181 134 0.04261909 AGPAT5 1-acylglycerol-3 -phosphate O-acyltransferase 5 1.180946 0.04081501 (lysophosphatidic acid acyltransferase, epsilon) N4BP1 NEDD4 binding protein 1 1.180702 0.04692864 L3MBTL2 l(3)mbt-like 2 (Drosophila) 1.180026 0.0299198 ADAM30 ADAM metallopeptidase domain 30 1.179 0.04990268 SHPRH SNF2 histone linker PHD RING helicase 1.178229 0.00451453 SMARCA SWI/SNF related, matrix associated, actin 1.177293 0.013042 1 dependent regulator of chromatin, subfamily a, member 1 TOMM70 translocase of outer mitochondrial membrane 70 1.176887 0.03478562 A homolog A (S. cerevisiae) TMEM50 transmembrane protein 5OA 1.174488 0.04619627 A RPL14 ribosomal protein L14 1.174045 0.03528184 MMP 13 matrix metallopeptidase 13 (collagenase 3) 1.173405 0.0121 2002 SNRK SNF related kinase 1.173346 0.01573733 CCDC7 coiled-coil domain containing 7 1.171795 0.01953617 GIMAP8 GTPase, IMAP family member 8 1.171424 0.04639992 UTP20 UTP20, small subunit (SSU) processome 1.171 1 0.02999942 component, homolog (yeast) SCAPER S-phase cyclin A-associated protein in the ER 1.170871 0.03165583 CDH6 cadherin 6, type 2, K-cadherin (fetal kidney) 1.170618 0.04588459 TFPI tissue factor pathway inhibitor (lipoprotein- 1.170572 0.03900407 associated coagulation inhibitor) C6orfl25 Chromosome 6 open reading frame 125 1.170359 0.01194836 UBE3B ubiquitin protein ligase E3B 1.169829 0.01247029 C12orfl0 chromosome 12 open reading frame 10 1.169491 0.03108954 RAD50 RAD50 homolog (S. cerevisiae) 1.168972 0.04507372 SRRT serrate RNA effector molecule homolog 1.168708 0.04933513 (Arabidopsis) DNTT deoxynucleotidyltransferase, terminal 1.168405 0.02438835 C6orfl 82 Chromosome 6 open reading frame 182 1.1 67525 0.008980 1 UGT2A1 UDP glucuronosyltransferase 2 family, 1.167157 0.00153427 polypeptide A l RPL27A ribosomal protein L27a 1.16714 0.03286277 C9orf86 chromosome 9 open reading frame 86 1.166704 0.00822025 ZBTB7A zinc finger and BTB domain containing 7A 1.166621 0.00152025 CISD2 CDGSH iron sulfur domain 2 1.165899 0.02019682 ITGB4 integrin, beta 4 1.164572 0.04837165 C10orf53 chromosome 10 open reading frame 53 1.161286 0.03491949 GLOl glyoxalase 1.160551 0.04744756 SLC15A1 solute carrier family 15 (oligopeptide transporter), 1.159201 0.04679593 member 1 GMCL1 germ cell-less homolog 1 (Drosophila) 1.158554 0.03783874 DNAJB1 1 DnaJ (Hsp40) homolog, subfamily B, member 11 1.158226 0.03171 122 DB1/ 694 3 7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest Symbol Change value USOl USOl vesicle docking protein homolog (yeast) 1.157228 0.03036641 PSMD1 proteasome (prosome, macropain) 26S subunit, 1.156795 0.03019009 non-ATPase, 1 SLFN12 #N/A 1.153905 0.02544823 HDDC2 HD domain containing 2 1.153537 0.00641685 ST6GAL1 ST6 beta-galactosamide alpha-2,6-sia]yltranferase 1.152772 0.03156348 1 TJAP1 tight junction associated protein 1 (peripheral) 1.152616 0.01205789 KEL Kell blood group, metallo-endopeptidase 1.152594 0.0401423 TSC22D1 TSC22 domain family, member 1 1.152544 0.04055428 LZIC leucine zipper and CTNNBIP 1 domain containing 1.152433 0.01 022804 ATG3 ATG3 autophagy related 3 homolog (S. cerevisiae) 1.151769 0.04771406 PI 3CD phosphoinositide-3 -kinase, catalytic, delta 1.150789 0.03397076 polypeptide

Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones. Data Set P-value Detailed Description 1. Lactate-Specific Genes Stem Cells Enriched in mouse neural stem cells, compared to differentiated STEMCELL NEURAL UP 1.31E-13 brain Enriched in mouse embryonic stem cells, compared to differentiated brain and bone STEMCELL EMBRYONIC UP 3.60E-08 marrow cells DNA Damage Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 UVC TTD ALL DN 2.83E-07 J/m 2 UVC Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 UVC XPCS ALL DN 7.98E-07 J/m 2 UVC Down-regulated at 8 hours following treatment of XPB/CS UVC XPCS 8HR DN 1.94E-06 fibroblasts with 3 J/m 2 UVC Down-regulated at 4 hours following treatment of XPB/TTD fibroblasts with 3 UVC TTD 4HR DN 2.93E-06 J/m 2 UVC Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD UVC_TTD-XPCS_COMMON_DN 4.98E-05 fibroblasts with 3 J/m 2 UVC UVC HIGH ALL DN 1.24E-03 Down-regulated at any

DBl/ 69437516.1 Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones. Data Set P-value Detailed Description timepoint following treatment of WS1 human skin fibroblasts with UVC at a high dose (50 J/m 2) (clusters dl-d9) Key Transcription Factors Neighborhood of HDAC2 histone deacetylase 2 in the MORF HDAC2 219 3.1 E-06 MORF expression compendium Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC- associated zinc finger protein (purine-binding transcription GGGAGGRR_V$MAZ_Q6 1.02E-04 factor) Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif SCGGAAGY which matches annotation for ELK1: ELK1 , member of ETS oncogene SCGGAAGY V$ELK1 02 1.47E-04 family Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTTSGCGSG which matches annotation for E2F
TFDP1 : transcription factor Dp- V$E2F1_Q4_01 3.28E-04 1 Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax TTGTTT_V$FOX04 homolog, Drosophila); 0 1 3.72E-04 translocated to, 7 Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl GGGCGGR_V$SP1_Q6 .75E-04 transcription factor Cancer Prognosis (Poor Survival) Genes overexpressed in TACI low patients (poor prognosis in MOREAUX TACI HI VS LOW DN 1.43E-04 multiple myeloma) 1/ 69437516.1 _ _ _ - Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones. Data Set P-value Detailed Description Genes highly expressed in HCC SURVIVAL GOOD VS POOR D hepatocellular carcinoma with N poor survival. 2. Ketone-Specific Genes Stem Cells Enriched in mouse hematopoietic stem cells, STEMCELL HEMA compared to differentiated brain TOPOIETIC_UP and bone marrow Key Transcription Factors Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer CAGGTG_V$E12_Q6 7.97E-05 binding factors E12/E47) Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TGACAGNY which matches annotation for MEIS1: Meisl, myeloid ecotropic viral integration site 1 homolog TGACAGNY V$MEIS1 0 1 3.33E-04 (mouse) Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGTGGRR which matches annotation for PAX4: paired GGGTGGRR V$PAX4 03 4.16E-04 box gene 4 Neighborhood of ATF2 activating transcription factor 2 in the MORF expression MORF ATF2 258 8.02E-04 compendium 3. Common Intersecting Genes (Upregulated by both Lactate and Ketones) DNA Damage Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 UVC XPCS ALL DN 2.60E-13 J/m 2 UVC Down-regulated at 8 hours following treatment of XPB/CS UVC XPCS 8HR DN 7.33E-12 fibroblasts with 3 J/m 2 UVC Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 UVC TTD ALL DN 2.47E-08 J/m 2 UVC UVC XPCS 4HR DN 3.21E-07 Down-regulated at 4 hours DBl/ 69437516.1 Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones. Data Set P-value Detailed Description following treatment of XPB/CS fibroblasts with 3 J/m 2 UVC Down-regulated at 4 hours following treatment of XPB/TTD fibroblasts with 3 UVC TTD 4HR DN 3.38E-07 J/m 2 UVC Downregulated by UV-B light in normal human epidermal UVB NHEK1 DN 2.68E-06 keratinocytes Down-regulated at 8 hours following treatment of XPB/TTD fibroblasts with 3 UVC TTD 8HR DN 1.27E-05 J/m 2 UVC Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD UVC TTD-XPCS COMMON DN 6.54E-04 fibroblasts with 3 J/m 2 UVC Regulated by UV-B light in normal human epidermal UVB_NHEK3_C5 9.27E-04 keratinocytes, cluster 5 Stem Cells Enriched in mouse embryonic stem cells, compared to differentiated brain and bone STEMCELL EMBRYONIC UP 7.26E-08 marrow cells Enriched in mouse neural stem cells, compared to differentiated STEMCELL NEURAL UP 1.29E-07 brain and bone marrow cells Enriched in mouse hematopoietic stem cells, compared to differentiated brain STEMCELL HEMATOPOIETIC UP 2.93E-06 and bone marrow Key Transcription Factors Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl GGGCGGR_V$SP1_Q6 1.16E-07 transcription factor Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer CAGGTG_V$E12_Q6 1.30E-06 binding factors E12/E47) Genes with promoter regions [- 2kb,2kb] around transcription TGGAAA V$NFAT Q4 0 1 6.09E-06 start site containing the motif DBl/ 69437516.1 ~ - _ Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones. Data Set P-value Detailed Description TGGAAA which matches annotation for FAT
NFATC Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid CTTTGT_V$LEF 1 Q2 1.61E-05 enhancer-binding factor 1 Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); TTGTTT_V$FOXO4_0 7.86E-05 translocated to, 7 Cancer Associated Genes Genes whose expression is consistently negatively correlated with estrogen receptor status in breast cancer - higher expression is associated BRCA ER NEG 3.48E-04 with ER-negative tumors Genes whose expression is consistently positively correlated with estrogen receptor status in breast cancer - higher expression is associated BRCAJER POS 6.77E-04 with ER-positive tumors Cancer related genes involved BRENTANI SIGNALING .05E-03 in the cell signaling

Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ubiquitin-conjugating enzyme E2D 2 UBE2D2 (UBC4/5 homolog, yeast) 11.637619 0.00544828 SRP19 signal recognition particle 19kDa 8.965928 0.00278124 EIF5B eukaryotic translation initiation factor 5B 8.853053 0.04053256 RAPIA RAPIA, member of RAS oncogene family 4.430772 0.01890408 CHMP2B chromatin modifying protein 2B 6.857511 0.03281982 PRDX1 peroxiredoxin 1 6.15612 0.02465945 SMC4 structural maintenance of chromosomes 4 4.707114 0.03654239 Rho-associated, coiled-coil containing ROCK2 protein kinase 2 5.852909 0.03308627

DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value BCLAF1 BCL2-associated transcription factor 1 5.819574 0.00240797 ubiquitin-conjugating enzyme E2D 3 UBE2D3 (UBC4/5 homolog, yeast) 5.713108 0.021 14428 METTL5 methyltransferase like 5 4.101808 0.01369737 CCNG1 cyclin Gl 5.586583 0.01011364 YBX1 Y box binding protein 1 5.455093 0.00261863 NMD3 NMD3 homolog (S. cerevisiae) 5.436879 0.00447774 MTDH metadherin 5.228131 0.01520368 LXN latexin 5.025051 0.00486952 H3F3A H3 histone, family 3A 5.188202 0.0162106 SPAST spastin 5.161775 6.01E-05 PPIG peptidylprolyl isomerase G (cyclophilin G) 5.060878 0.04469338 SNX2 sorting nexin 2 4.989412 0.03586009 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX46 46 4.96017 0.03654288 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily SMARCA5 a, member 5 4.842003 0.0187601 protein phosphatase 1, catalytic subunit, beta PPPICB isozyme 2.468217 0.04691501 LRPPRC leucine-rich PPR-motif containing 4.564774 0.04328232 KDEL (Lys-Asp-Glu-Leu) endoplasmic KDELR2 reticulum protein retention receptor 2 3.368323 0.04949704 ASF1 anti-silencing function 1 homolog A ASF1A (S. cerevisiae) 4.469944 0.01353041 IVNS1ABP influenza virus NS A binding protein 4.458858 0.04032226 NIPBL Nipped-B homolog (Drosophila) 4.448285 0.02143111 P pinin, desmosome associated protein 4.433149 0.00780293 TCERG1 transcription elongation regulator 1 3.545678 0.04063693 TOP2B topoisomerase (DNA) II beta 180kDa 2.823094 0.02218412 ZMYM4 zinc finger, MYM-type 4 4.267182 0.01393137 SFRS3 splicing factor, arginine/serine-rich 3 2.716461 0.03522487 LAPTM4A lysosomal protein transmembrane 4 alpha 4.093129 0.00222108 translocated promoter region (to activated TPR MET oncogene) 4.08363 0.00433995 CCNI cyclin I 4.045976 0.02394342 proteasome (prosome, macropain) 26S PSMD1 subunit, non-ATPase, 1 4.011931 0.00720011 proteasome (prosome, macropain) 26S PSMC2 subunit, ATPase, 2 3.987502 0.00426193 RWDD4A RWD domain containing 4A 3.882013 0.02249924 Rho-associated, coiled-coil containing ROCK1 protein kinase 1 3.257404 0.01235219 NOP58 NOP58 ribonucleoprotein homolog (yeast) 3.788493 0.00288593 EPHB4 EPH receptor B4 3.78501 0.02475939 EPRS glutamyl-prolyl-tRNA synthetase 2.662763 0.04513234 protein tyrosine phosphatase type IVA, PTP4A1 member 1 2.270167 0.00847749 ABCE1 ATP-binding cassette, sub-family E (OABP), 1.937131 0.02691982 DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value member 1 protein kinase, cAMP-dependent, regulatory, PRKAR1A type I, alpha (tissue specific extinguisher 1) 3.700851 0.00533686 mitogen-activated protein kinase kinase MAP4K3 kinase kinase 3 3.183468 0.02370712 chromodomain helicase DNA binding CHD1 protein 1 2.27918 0.02465009 MY06 myosin VI 1.499933 0.04628552 BIRC6 baculoviral IAP repeat-containing 6 3.656537 0.01040232 FIP1L1 FI like 1 (S. cerevisiae) 3.647902 0.0419402 UGDH UDP-glucose 6-dehydrogenase 3.642483 0.02673765 HDLBP high density lipoprotein binding protein 1.923995 0.0317557 acyl-CoA dehydrogenase, C-4 to C-12 ACADM straight chain 3.582422 0.04333075 RFWD2 ring finger and WD repeat domain 2 3.566507 0.03374643 TXNDC9 thioredoxin domain containing 9 3.559682 0.02318797 far upstream element (FUSE) binding protein FUBP1 1 2.584276 0.02883731 DLD dihydrolipoamide dehydrogenase 3.54755 0.03042714 FBXW11 F-box and WD repeat domain containing 11 3.538266 0.01890564 HSPA4 heat shock 70kDa protein 4 3.534902 0.02613913 chaperonin containing TCP1, subunit 6A CCT6A (zeta 1) 2.226682 0.02645749 guanine nucleotide binding protein-like 2 GNL2 (nucleolar) 3.497915 0.01416406 ZNF259 zinc finger protein 259 3.457681 0.04340342 RANBP9 RAN binding protein 9 3.400619 0.00125475 TCEA1 transcription elongation factor A (SII), 1 3.391912 0.03816125 PPID peptidylprolyl isomerase D 3.355162 0.01495089 RNF8 ring finger protein 8 3.3143 0.00922491 SWI/SNF-related, matrix-associated actin- dependent regulator of chromatin, subfamily SMARCAD1 a, containing DEAD/H box 1 3.284105 0.04696085 POLR1A polymerase (RNA) I polypeptide A, 94kDa 1.241458 0.0372547 SMC6 structural maintenance of chromosomes 6 2.772324 0.01058738 CUL3 cullin 3 2.512555 0.03000904 CDV3 CDV3 homolog (mouse) 3.247154 0.0416902 SH3 domain binding glutamic acid-rich SH3BGRL protein like 3.242215 0.02599374 SMYD2 SET and MYND domain containing 2 2.182951 0.03899734 EEF2 eukaryotic translation elongation factor 2 3.218901 0.03839601 IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 2.915579 0.02633645 CAPN7 Calpain 7 3.213705 0.016063 succinate dehydrogenase complex, subunit SDHA A, flavoprotein (Fp) 3.197073 0.01758965 HAT1 histone acetyltransferase 1 3.188148 0.03486096 SQLE squalene epoxidase 3.159715 0.01084816 chaperonin containing TCP1, subunit 5 CCT5 (epsilon) 2.739476 0.00602847 DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value R F14 ring finger protein 14 3.131844 0.01 179033 HDAC2 histone deacetylase 2 1.713956 0.04708192 M-phase phosphoprotein 0 (U3 small MPHOSPH10 nucleolar ribonucleoprotein) 2.045137 0.0353561 mutS homolog 2, colon cancer, nonpolyposis MSH2 type 1 (E. coli) 2.98112 0.03627096 SF3B1 splicing factor 3b, subunit 1, 155kDa 3.079506 0.04359828 TCP1 t-complex 1 2.899216 0.02939434 HIBCH 3-hydroxyisobutyryl-Co A hydrolase 3.065273 0.01688263 guanine nucleotide binding protein (G GNB1 protein), beta polypeptide 1 3.050983 0.02355176 SP3 Sp3 transcription factor 3.033516 0.00452105 La ribonucleoprotein domain family, LARP7 member 7 3.023688 0.02499879 family with sequence similarity 98, member FAM98A A 2.506122 0.01 113668 MORF4L2 mortality factor 4 like 2 2.984871 0.03027653 nuclear casein kinase and cyclin-dependent NUCKS1 kinase substrate 1 2.746242 0.01 149953 CCNC cyclin C 2.948678 0.00690543 ENY2 enhancer of yellow 2 homolog (Drosophila) 2.948102 0.00070793 PRP4 pre-mRNA processing factor 4 PRPF4B homolog B (yeast) 2.165609 0.03223181 RAB10 RAB10, member RAS oncogene family 2.675383 0.00826866 SMT3 suppressor of if two 3 homolog 1 SUMOl (S. cerevisiae) 2.939321 0.01314778 SENP6 SUMOl/sentrin specific peptidase 6 2.92259 0.01329545 malic enzyme 1, NADP(+)-dependent, ME1 cytosolic 2.879955 0.00454168 CRTAP cartilage associated protein 1.943159 0.02923402 USP39 ubiquitin specific peptidase 39 2.866674 0.00731577 LTV1 LTV1 homolog (S. cerevisiae) 2.862159 0.03848354 MTIF2 mitochondrial translational initiation factor 2 1.631234 0.04677842 CCDC99 coiled-coil domain containing 99 2.834983 0.04509615 ZNF644 zinc finger protein 644 2.83475 0.02847176 UDP-GlcNAc:betaGal beta-l,3-N- B3GNT2 acetylglucosaminyltransferase 2 2.830064 0.02052011 SMC3 structural maintenance of chromosomes 3 2.825491 0.03046467 TBL1XR1 transducin (beta)-like 1 X-Iinked receptor 1 2.821702 0.01803827 COPG coatomer protein complex, subunit gamma 2.406812 0.03959455 DnaJ (Hsp40) homolog, subfamily B, DNAJB11 member 11 2.813687 0.01128434 BTF3 basic transcription factor 3 2.504564 0.04945883 USP34 ubiquitin specific peptidase 34 2.781149 0.03969944 RAS p21 protein activator (GTPase RASA1 activating protein) 1 2.760016 0.02594615 EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242 coatomer protein complex, subunit beta 2 COPB2 (beta prime) 1.897638 0.00131933 D / 6943751 6.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value CCAAT/enhancer binding protein (C/EBP), CEBPZ zeta 2.730668 0.04807979 SGOL1 shugoshin-like 1 (S. pombe) 2.730587 0.02367326 SEC63 SEC63 homolog (S. cerevisiae) 2.3961 0.00304391 HMGB2 high-mobility group box 2 1.972844 0.03882638 DYNC1I2 dynein, cytoplasmic 1, intermediate chain 2 1.410334 0.0279939 RWDD1 RWD domain containing 1 2.70643 0.03976333 PSIP1 PC4 and SFRS1 interacting protein 1 2.704173 0.00379656 TRIO triple functional domain (PTPRF interacting) 1.971861 0.04525982 PPIC peptidylprolyl isomerase C (cyclophilin C) 2.684486 0.01273313 ATPase, H+ transporting, lysosomal 42kDa, ATP6V1C1 VI subunit Cl 2.667986 0.01481745 RARS arginyl-tRNA synthetase 1.592423 0.02013136 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX18 18 2.65979 0.0499591 1 TOPBP1 topoisomerase (DNA) II binding protein 1 2.659609 0.01512887 UNC50 unc-50 homolog (C. elegans) 2.129257 0.03952495 excision repair cross-complementing rodent ERCC5 repair deficiency, complementation group 5 2.64652 0.03234078 ZNF326 Zinc finger protein 326 2.639598 0.00776776 LAMC1 laminin, gamma 1 (formerly LAMB2) 2.186259 0.01464433 PDLIM7 PDZ and LIM domain 7 (enigma) 1.560624 0.01849702 RFC1 replication factor C (activator 1) 1, 145kDa 2. 16992 0.00583182 SF3B5 splicing factor 3b, subunit 5, lOkDa 2.593595 0.01024026 ANKRD17 ankyrin repeat domain 17 2.592918 0.00227678 ARF4 ADP-ribosylation factor 4 2.58944 0.01239217 TRAF family member-associated NFKB TANK activator 2.583302 0.02722171 CSNK1A1 casein kinase 1, alpha 1 2.565332 0.02008984 NCOR1 nuclear receptor co-repressor 1 1.264318 0.04431849 epidermal growth factor receptor pathway EPS8 substrate 8 2.029185 0.01334663 caspase 2, apoptosis-related cysteine CASP2 peptidase 2.555936 0.0459927 PNPT1 polyribonucleotide nucleotidyltransferase 1 1.565445 0.03732588 RAB1A RAB1A, member RAS oncogene family 2.373609 0.04191459 proteasome (prosome, macropain) 26S PSMD14 subunit, non-ATPase, 1 2.533865 0.02390241 NOTCH3 Notch homolog 3 (Drosophila) 2.518418 0.02050312 SRPK2 SFRS protein kinase 2 1.22325 0.01501723 MRPL3 mitochondrial ribosomal protein L3 2.298195 0.03084317 PLK4 polo-like kinase 4 (Drosophila) 2.510571 0.02626713 ARP3 actin-related protein 3 homolog ACTR3 (yeast) 2.500061 0.02540777 MOB1, Mps One Binder kinase activator¬ MOBKL1A like 1A (yeast) 2.495315 0.01061014 USP3 ubiquitin specific peptidase 3 2.491308 0.03275649 glycerol-3-phosphate dehydrogenase 2 GPD2 (mitochondrial) 2.471884 0.03872717 DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value STK38 serine/threonine kinase 38 1.642924 0.016321 12 solute carrier family 39 (zinc transporter), SLC39A6 member 6 1.22186 0.0061314 synaptotagmin binding, cytoplasmic R A SYNCRIP interacting protein 1.957398 0.0125552 CLIC4 chloride intracellular channel 4 2.420927 0.04525662 ZNF639 zinc finger protein 639 1.539132 0.03676195 CCND1 Cyclin Dl 1.930024 0.02353764 TAGLN2 transgelin 2 2.407305 0.03670214 nucleophosmin (nucleolar phosphoprotein NPM1 B23, numatrin) 2.406641 0.01665033 GRN granulin 1.493607 0.03683456 Proteasome (prosome, macropain) 26S PSMD6 subunit, non-ATPase, 6 2.138274 0.03380946 LIM and senescent cell antigen-like domains LIMS1 1 1.72779 0.04472927 KIF2C kinesin family member 2C 2.338823 0.02722488 phosphoinositide-3 -kinase, catalytic, alpha PIK3CA polypeptide 1.728352 0.03384356 AK2 adenylate kinase 2 2.32623 0.04153099 BCAP29 B-cell receptor-associated protein 29 1.927448 0.02335138 polycystic kidney disease 2 (autosomal PKD2 dominant) 2.312196 0.00272198 PDCD6IP programmed cell death 6 interacting protein 1.970203 0.00643999 PCBP4 poly(rC) binding protein 4 2.297239 0.0480034 IMMT inner membrane protein, mitochondrial 2.291678 0.02551435 Stress-associated endoplasmic reticulum SERP1 protein 1 1.536698 0.00112698 transforming, acidic coiled-coil containing TACC3 protein 3 2.268162 0.01045492 MTX1 metaxin 1 2.240865 0.04610751 TBC1 (tre-2/USP6, BUB2, cdcl6) domain TBC1D1 family, member 1 2.235136 0.00238682 TFB2M transcription factor B2, mitochondrial 2.068018 0.035821 3 SCARB2 scavenger receptor class B, member 2 2.225542 0.00468326 KPNA1 karyopherin alpha 1 (importin alpha 5) 2.225491 0.02352899 mitogen-activated protein kinase kinase MAP4K4 kinase kinase 4 2.068156 0.00788839 PKN2 protein kinase N2 1.81078 0.03572897 USP1 ubiquitin specific peptidase 1 2.204293 0.02425862 succinate-CoA ligase, ADP-forming, beta SUCLA2 subunit 2.0281 1 0.02841861 3-hydroxy-3-methylglutaryl-CoA synthase 1 HMGCS1 (soluble) 2.202971 0.04764687 PPIE peptidylprolyl isomerase E (cyclophilin E) 2.202103 0.0337451 1 ADP-ribosylation factor guanine nucleotide- ARFGEF1 exchange factor l(brefeldin A-irihibited) 2.200694 0.03552716 STT3, subunit of the STT3B oligosaccharyltransferase complex, homolog 2.199036 0.03541682 DB1/ 694 37516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value B (S. cerevisiae) SFRS1 1 splicing factor, arginine/serine-rich 11 2.197102 0.03128218 ZNF281 zinc finger protein 28 2.19509 0.01743985 mutL homolog 1, colon cancer, nonpolyposis MLH1 type 2 (E. coli) 2.1927 0.00460208 TMEM70 transmembrane protein 70 2.18302 0.01 154643 TTC1 tetratricopeptide repeat domain 1 2.063528 0.04752468 SEC31A SEC31 homolog A (S. cerevisiae) 2.1652 0.02487707 hypoxia inducible factor 1, alpha subunit HIF1A (basic helix-loop-helix transcription factor) 1.591415 0.00884964 SEC24B SEC24 family, member B (S. cerevisiae) 2.151645 0.01992121 EIF4E eukaryotic translation initiation factor 4E 2.049544 0.0267098 ACTL6A actin-like 6A 1.640505 0.04155384 solute carrier family 35 (CMP-sialic acid SLC35A1 transporter), member Al 1.492421 0.03009839 SLBP stem-loop binding protein 1.980568 0.02420595 IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745 protein disulfide isomerase family A, PDIA6 member 6 1.533451 0.01326546 SMAP1 small ArfGAP 1 2.089852 0.00484321 DTL denticleless homolog (Drosophila) 1.436258 0.00228503 YIPF5 Yipl domain family, member 5 2.076073 0.03670269 asp (abnormal spindle) homolog, ASPM microcephaly associated (Drosophila) 1.803894 0.04304251 RRM2 ribonucleotide reductase M2 2.012222 0.02429985 protein phosphatase 1, regulatory (inhibitor) PPP1R15B subunit B 2.067971 0.00766167 HTATSF1 HIV-1 Tat specific factor 1 2.065056 0.04590911 NAV2 neuron navigator 2 2.05691 0.03319842 isocitrate dehydrogenase 1 (NADP+), IDH1 soluble 2.052557 0.02683413 BAX BCL2-associated X protein 2.048317 0.039567 PMPCB peptidase (mitochondrial processing) beta 2.037316 0.0072201 MRPS2 Mitochondrial ribosomal protein S2 2.036969 0.01324621 MRPL9 mitochondrial ribosomal protein L9 2.03358 0.0281763 TNPOl transportin 1 2.03241 1 0.03457859 MOCO sulphurase C-terminal domain MOSC2 containing 2 2.027181 0.00651172 PPP4R2 Protein phosphatase 4, regulatory subunit 2 2.027077 0.02103272 ARP2 actin-related protein 2 homolog ACTR2 (yeast) 2.013524 0.01953361 leucine zipper-EF-hand containing LETM1 transmembrane protein 1 1.698753 0.02155205 guanine nucleotide binding protein-like 3 GNL3 (nucleolar) 2.005014 0.01735622 DECPvl 2,4-dienoyl CoA reductase , mitochondrial 2.00651 1 0.02598747 AQR aquarius homolog (mouse) 1.544351 0.01005732 capping protein (actin filament) muscle Z- CAPZA1 line, alpha 1 2.003944 0.00987919 DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value FH fumarate hydratase 1.987209 0.01470817 MRPS5 mitochondrial ribosomal protein S5 1.641288 0.02848696 LIMD1 LIM domains containing 1 1.390887 0.01945038 THUMPD3 THUMP domain containing 3 1.798321 0.02891873 nuclear autoantigenic sperm protein (histone- NASP binding) 1.586624 0.02198518 WDR26 WD repeat domain 26 1.766404 0.04389929 heterogeneous nuclear ribonucleoprotein L- HNRPLL like 1.965554 0.02133848 WTAP Wilms tumor 1 associated protein 1.777876 0.00868387 LSM3 homolog, U6 small nuclear RNA LSM3 associated (S. cerevisiae) 1.95834 0.040095 HDAC1 histone deacetylase 1 1.957793 0.0333261 1 ZMAT3 zinc finger, matrin type 3 1.954859 0.02830097 GYS1 glycogen synthase 1 (muscle) 1.207255 0.0073425 R F2 ring finger protein 2 1.951609 0.00229371 FOXN2 forkhead box N2 1.948693 0.00671655 RAB23 RAB23, member RAS oncogene family 1.52539 0.01869873 SNX5 sorting nexin 5 1.941349 0.00305077 GDI2 GDP dissociation inhibitor 2 1.939501 0.0168794 SPATA5 Spermatogenesis associated 5 1.938449 0.01321604 MRPL37 mitochondrial ribosomal protein L3 1.265484 0.03009753 APEX nuclease (multifunctional DNA repair APEX1 enzyme) 1 1.937633 0.01208949 CDK8 cyclin-dependent kinase 8 1.937355 0.03136558 NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931 HINT1 histidine triad nucleotide binding protein 1 1.210712 0.04891515 ITSN1 intersectin 1 (SH3 domain protein) 1.920858 0.04228789 BLZF1 basic leucine zipper nuclear factor 1 1.920386 0.01207716 Ctr9, Pafl/RNA polymerase II complex CTR9 component, homolog (S. cerevisiae) 1.911411 0.00146435 SLTM SAFB-like, transcription modulator 1.495363 0.02071 192 KPNA3 karyopherin alpha 3 (importin alpha 4) 1.382818 0.0289694 STX7 syntaxin 7 1.888885 0.02528416 NBR1 neighbor of BRCA1 gene 1 1.888532 0.01926365 EVI5 ecotropic viral integration site 5 1.883555 0.02040397 RPE ribulose-5-phosphate-3-epimerase 1.72725 0.04901899 proteasome (prosome, macropain) subunit, PSMB1 beta type, 1 1.877973 0.0332617 CAPN2 calpain 2, (m/II) large subunit 1.868506 0.02067163 N-acylsphingosine amidohydrolase (acid ASAH1 ceramidase) 1 1.273185 0.03366104 ubiquitin-fold modifier conjugating enzyme UFC1 1 1.294642 0.04198936 epithelial cell transforming sequence 2 ECT2 oncogene 1.412257 0.00609004 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, TAF9 32kDa 1.586724 0.04658612 DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value GNPDA1 glucosamine-6-phosphate deaminase 1 1.850039 0.01637317 GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.768741 0.03226337 protein-kinase, interferon-inducible double stranded RNA dependent inhibitor, repressor PRKRIR of (P58 repressor) 1.836748 0.03060855 proteasome (prosome, macropain) 26S PSMC1 subunit, ATPase, 1 1.83611 0.03905445 GYG1 glycogenin 1 1.833606 0.0066626 serine threonine kinase 39 (STE20/SPS1 STK39 homolog, yeast) 1.729703 0.04202932 KIAA1524 KIAA1524 1.24618 0.02323518 YAP1 Yes-associated protein 1 1.824953 0.04116296 proteasome (prosome, macropain) subunit, PSMA7 alpha type, 7 1.814899 0.0228106 NADH dehydrogenase (ubiquinone) 1, NDUFC1 subcomplex unknown, 1, 6kDa 1.814744 0.00472754 blocked early in transport 1 homolog (S. BET1 cerevisiae) 1.810406 0.04306222 protein tyrosine phosphatase, non-receptor PTPN9 type 9 1.806452 0.03400917 roundabout, axon guidance receptor, ROBOl homolog 1 (Drosophila) 1.802834 0.03733771 PIAS2 protein inhibitor of activated STAT, 2 1.475327 0.02186057 solute carrier family 1 (glutamate/neutral SLC1A4 amino acid transporter), member 4 1.794159 0.0013034 DnaJ (Hsp40) homolog, subfamily C, DNAJC13 member 13 1.616418 0.01480203 succinate-CoA ligase, GDP-forming, beta SUCLG2 subunit 1.786827 0.00924396 SAP30 Sin3A-associated protein, 30kDa 1.783367 0.04714102 SUZ12 suppressor of zeste 12 homolog (Drosophila) 1.781738 0.0427054 acidic (leucine-rich) nuclear phosphoprotein ANP32A 32 family, member A 1.773795 0.00540646 DDR1 discoidin domain receptor tyrosine kinase 1 1.769628 0.02493444 ZNF213 zinc finger protein 213 1.76888 0.02160061 down-regulator of transcription 1, TBP- DR1 binding (negative cofactor 2) 1.767005 0.02631065 PRKD1 protein kinase Dl 1.366096 0.02015636 RYK RYK receptor-like tyrosine kinase 1.751194 0.00185441 eukaryotic translation initiation factor 4 EIF4G1 gamma, 1 1.750254 0.00740522 Methylcrotonoyl-Coenzyme A carboxylase 1 MCCC1 (alpha) 1.746294 0.0228626 CCNB1 cyclin Bl 1.315053 0.02415274 mitogen-activated protein kinase kinase MAP3K7 kinase 7 1.743976 0.02238046 small nuclear ribonucleoprotein polypeptide SNRPC C 1.742362 0.04469681 UBA2 ubiquitin-like modifier activating enzyme 2 1.536631 0.03719408 DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ZZZ3 zinc finger, ZZ-type containing 3 1.36524 0.02901362 solute carrier family 30 (zinc transporter), SLC30A5 member 5 1.603386 0.01412032 CDC42SE1 CDC42 small effector 1 1.524227 0.02124608 amylo-alpha-1, 6-glucosidase, 4-alpha- AGL glucanotransferase 1.305308 0.02445334 inhibitor of Bruton agammaglobulinemia IBTK tyrosine kinase 1.625579 0.01834248 FIGNL1 fidgetin-like 1 1.724436 0.041 13886 budding uninhibited by benzimidazoles 1 BUB1 homolog (yeast) 1.272392 0.01439459 GNPAT glyceronephosphate O-acyltransferase 1.167893 0.02519736 PRP38 pre-mRNA processing factor 38 PRPF38A (yeast) domain containing A 1.267458 0.0372219 ER degradation enhancer, mannosidase EDEM3 alpha-like 3 1.356732 0.04196012 PHTF2 Putative homeodomain transcription factor 2 1.498429 0.01305125 YTHDF3 YTH domain family, member 3 1.548102 0.02135835 PRKD3 protein kinase D3 1.302343 0.04005699 NIT2 nitrilase family, member 2 1.697659 0.03895012 translocase of outer mitochondrial membrane TOMM70A 70 homolog A (S. cerevisiae) 1.442531 0.03272251 CENPK centromere protein K 1.364588 0.03575031 protein phosphatase 1, regulatory (inhibitor) PPP1R2 subunit 2 1.693178 0.00191476 CPNE3 copine III 1.691682 0.00274705 procollagen-lysine, 2-oxoglutarate 5- PLOD3 dioxygenase 3 1.342835 0.02428522 C8or03 chromosome 8 open reading frame 33 1.689323 0.0139295 DAP death-associated protein 1.688477 0.00441882 CDC5L CDC5 cell division cycle -like (S. pombe) 1.686596 0.00513394 DnaJ (Hsp40) homolog, subfamily B, DNAJB6 member 6 1.68511 0.02203927 DnaJ (Hsp40) homolog, subfamily C, DNAJC10 member 10 1.229817 0.03064105 chaperonin containing TCP1, subunit 3 CCT3 (gamma) 1.663267 0.04685597 UTP18, small subunit (SSU) processome UTP18 component, homolog (yeast) 1.23789 0.01561913 RAD17 RAD 17 homolog (S. pombe) 1.601375 0.0208996 ribosome binding protein 1 homolog 180kDa RRBP1 (dog) 1.676273 0.03208152 QARS glutaminyl-tRNA synthetase 1.580939 0.0125861 1 PTPRJ protein tyrosine phosphatase, receptor type, J 1.360438 0.03523859 USP24 ubiquitin specific peptidase 24 1.317279 0.04933808 ELAV (embryonic lethal, abnormal vision, ELAVL1 Drosophila)-like 1 (Hu antigen R) 1.640597 0.03564955 ACTB actin, beta 1.633494 0.04468234 NCAPH non-SMC condensin I complex, subunit H 1.370164 0.01932908 1/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ORMDL1 ORMl-like 1 (S. cerevisiae) 1.54414 0.02275899 UDP-N-acetyl-alpha-D- galactosaminerpolypeptide N- acetylgalactosaminyltransferase 1 (GalNAc- GALNT1 Tl) 1.626164 0.03763074 TMEM30A transmembrane protein 3OA 1.62414 0.00774066 OXCT1 3-oxoacid CoA transferase 1 1.261625 0.02520766 LTA4H leukotriene A4 hydrolase 1.386545 0.03548382 DEAD (Asp-Glu-Ala-Asp) box polypeptide DDX41 4 1 1.613103 0.01994811 TM9SF2 transmembrane 9 superfamily member 2 1.599129 0.0469163 DLL1 delta-like 1 (Drosophila) 1.343162 0.02388195 MFN1 mitofusin 1 1.251298 0.03838396 large subunit GTPase 1 homolog (S. LSG1 cerevisiae) 1.30556 0.02208307 RFC5 replication factor C (activator 1) 5, 36.5kDa 1.583884 0.00493414 LAP3 leucine aminopeptidase 3 1.260347 0.04343932 solute carrier family 4, sodium bicarbonate SLC4A7 cotransporter, member 7 1.200374 0.01216306 GGCX gamma-glutamyl carboxylase 1.38939 0.0460239 carboxyl ester lipase (bile salt-stimulated CEL lipase) 1.568045 0.03937509 INTS7 integrator complex subunit 7 1.563662 0.04482643 MTMR10 myotubularin related protein 10 1.561932 0.0103955 APAF1 apoptotic peptidase activating factor 1 1.306905 0.03041618 E2F5 E2F transcription factor 5, pl30-binding 1.549601 0.03693464 BTB and CNC homology 1, basic leucine BACH1 zipper transcription factor 1 1.234722 0.01598341 protein tyrosine phosphatase, non-receptor PTPN2 type 2 1.54739 0.02035435 diacylglycerol O-acyltransferase homolog 1 DGAT1 (mouse) 1.54416 0.01906196 CPT1A carnitine palmitoyltransferase 1A (liver) 1.541995 0.0455955 ZNF35 zinc finger protein 3 1.462328 0.01374461 minichromosome maintenance complex MCM3 component 3 1.204643 0.02501993 SRR serine racemase 1.451819 0.03543625 PPA2 pyrophosphatase (inorganic) 2 1.533368 0.01586952 suppression of tumorigenicity 13 (colon ST13 carcinoma) (Hsp70 interacting protein) 1.392146 0.02567641 RGS7 regulator of G-protein signaling 7 1.528987 0.01630161 PCSK7 proprotein convertase subtilisin/kexin type 7 1.52515 0.00584015 WDR77 WD repeat domain 77 1.161034 0.0464362 calcium/calmodulin-dependent serine protein CASK kinase (MAGUK family) 1.509852 0.02504441 LAS1L LAS 1-like (S. cerevisiae) 1.523924 0.0047693 inner centromere protein antigens INCENP 135/155kDa 1.521596 0.00926599 COL1 1A1 collagen, type XI, alpha 1 1.358775 0.01500244 1 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ANGPTL4 Angiopoietin-like 4 1.36763 0.03038604 GUSB glucuronidase, beta 1.483723 0.00747287 MYO10 myosin X 1.361879 0.04208556 MID2 midline 2 1.500591 0.0169234 elongation factor Tu GTP binding domain EFTUD2 containing 2 1.454941 0.01886939 RNASEH2B ribonuclease H2, subunit B 1.499052 0.02568195 Neural precursor cell expressed, NEDD1 developmentally down-regulated 1 1.371 19 0.0359751 HTRA2 HtrA serine peptidase 2 1.381 117 0.04940812 tankyrase, TRF1 -interacting ankyrin-related TNKS2 ADP-ribose polymerase 2 1.413046 0.03105238 ITFG1 integrin alpha FG-GAP repeat containing 1 1.266819 0.01601937 CDH2 cadherin 2, type 1, N-cadherin (neuronal) 1.395061 0.04529743 SASH1 SAM and SH3 domain containing 1 1.404986 0.01632024 TYSND1 trypsin domain containing 1 1.470886 0.03841107 phospholipase A2, group VI (cytosolic, PLA2G6 calcium-independent) 1.465765 0.02742349 solute carrier family 5 (H+/peptide SLC15A2 transporter), member 2 1.314537 0.01002407 TM7SF3 transmembrane 7 superfamily member 3 1.388536 0.01990459 RBM8A RNA binding motif protein 8A 1.250975 0.00571058 phospholipase Dl, phosphatidylcholine- PLD1 specific 1.373202 0.04783635 SBF2 SET binding factor 2 1.453314 0.01078788 WEE1 WEE1 homolog (S. pombe) 1.401628 0.01546795 BRD7 bromodomain containing 7 1.448578 0.00933436 TMEM14C transmembrane protein 14C 1.447908 0.01223887 TRIM27 tripartite motif-containing 27 1.447185 0.04931129 family with sequence similarity 50, member FAM50A A 1.384223 0.02964922 DDHD1 DDHD domain containing 1 1.435652 0.02093535 SEC24C SEC24 family, member C (S. cerevisiae) 1.443774 0.03113679 ATP-binding cassette, sub-family A (ABCl), ABCA1 member 1 1.366742 0.00856212 EPAS1 endothelial PAS domain protein 1 1.437838 0.02537747 RNASEH2C ribonuclease H2, subunit C 1.436884 0.04326723 nuclear receptor subfamily 1, group H, NR1H4 member 4 1.43593 0.01391427 nucleolar complex associated 4 homolog (S. NOC4L cerevisiae) 1.335968 0.0161945 FHL1 four and a half LIM domains 1 1.282345 0.00644461 HSDL2 hydroxysteroid dehydrogenase like 2 1.250353 0.0421 176 dihydrolipoamide branched chain DBT transacylase E2 1.298264 0.03189072 UBE2Z ubiquitin-conjugating enzyme E2Z 1.424388 0.04566522 VAC 14 Vacl4 homolog (S. cerevisiae) 1.422842 0.03352068 vacuolar protein sorting 53 homolog (S. VPS53 cerevisiae) 1.421566 0.04694093 1/ 694 3 7516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ectonucleoside triphosphate ENTPD5 diphosphohydrolase 5 1.419164 0.02048402 CKMT2 creatine kinase, mitochondrial 2 (sarcomeric) 1.414046 0.0128032 nudix (nucleoside diphosphate linked moiety NUDT21 X)-type motif 2 1 1.249476 0.04665571 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) EGFR oncogene homolog, avian) 1.166192 0.04292096 MEIS1 Meis homeobox 1 1.400454 0.04054264 retinol dehydrogenase 11 (all-trans/9-cis/l 1- RDH11 cis) 1.397657 0.0050891 SNAP23 synaptosomal-associated protein, 23kDa 1.330166 0.03566571 translocase of inner mitochondrial membrane TIMM44 44 homolog (yeast) 1.394702 0.02292879 ATP-binding cassette, sub-family F ABCF2 (GCN20), member 2 1.394627 0.03672061 eukaryotic translation initiation factor 2- EIF2AK3 alpha kinase 3 1.298331 0.04888608 PAK1IP1 PA 1 interacting protein 1 1.26866 0.0392548 BLM Bloom syndrome, RecQ helicase-like 1.392962 0.02331052 BAG2 BCL2-associated athanogene 2 1.390864 0.00399346 SYTL4 synaptotagmin-like 4 1.387118 0.02970297 PNKD Paroxysmal nonkinesigenic dyskinesia 1.304131 0.02809504 USP38 ubiquitin specific peptidase 38 1.37522 0.04727816 inositol polyphosphate- 5-phosphatase, INPP5D 145kDa 1.374524 0.00364048 caspase 6, apoptosis-related cysteine CASP6 peptidase 1.372269 0.04203738 ADAM28 ADAM metallopeptidase domain 28 1.277873 0.00355689 NGFI-A binding protein 2 (EGR1 binding NAB2 protein 2) 1.364006 0.02567161 NPC1 Niemann-Pick disease, type C I 1.362315 0.04477366 ADAMDEC1 ADAM-like, decysin 1 1.362129 0.03679769 PELI1 pellino homolog 1 (Drosophila) 1.35374 0.01691951 DAP3 death associated protein 3 1.271808 0.02339598 LIG1 ligase I, DNA, ATP-dependent 1.268785 0.01252088 CDCA8 Cell division cycle associated 8 1.340746 0.04499828 ROD1 regulator of differentiation 1 (S. ROD1 pombe) 1.200754 0.0474292 E2F8 E2F transcription factor 8 1.232086 0.00048585 cyclin-dependent kinase inhibitor 2C (pi 8, CDKN2C inhibits CD 4) 1.33462 0.04260088 I PPL1 inositol polyphosphate phosphatase-like 1 1.329887 0.00979076 TSPAN12 tetraspanin 2 1.211375 0.02651059 NSUN4 NOP2/Sun domain family, member 4 1.327342 0.03660922 HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.258927 0.00915241 serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen SERPINHl binding protein 1) 1.32396 0.01919945 DBl/ 69437516.1 Supplemental Table 4 : Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells Fold Ttest P Gene Symbol Gene Description Change value ABHD5 abhydrolase domain containing 5 1.259035 0.00596344 MDFIC MyoD family inhibitor domain containing 1.242969 0.03261241 SMO smoothened o olog (Drosophila) 1.320865 0.03439192 C14orfl47 chromosome 14 open reading frame 147 1.319192 0.03875552 R F26 ring finger protein 26 1.242143 0.04297931 C3orf58 chromosome 3 open reading frame 58 1.259091 0.04608467 A2M alpha-2-macroglobulin 1.293429 0.00961782 FBXW2 F-box and WD repeat domain containing 2 1.284946 0.03658627 SFRS16 splicing factor, arginine/serine-rich 16 1.289527 0.00918842 eukaryotic translation elongation factor 1 EEF1D delta (guanine nucleotide exchange protein) 1.299174 0.02232024 DIDOl death inducer-obliterator 1 1.28637 0.02217596 WDR46 WD repeat domain 46 1.179087 0.01295145 cleavage stimulation factor, 3' pre-RNA, CSTF2 subunit 2, 64kDa 1.283423 0.02479593 TPMT thiopurine S-methyltransferase 1.282727 0.0166767 ATPase, H+ transporting, lysosomal ATP6V1H 50/57kDa, VI subunit H 1.211331 0.026815 origin recognition complex, subunit 1-like ORC1L (yeast) 1.273124 0.03331651 protein tyrosine phosphatase, receptor type, PTPRA A 1.24583 0.00032856 platelet-activating factor acetylhydrolase lb, PAFAH1B3 catalytic subunit 3 (29kDa) 1.268768 0.02361777 SFXN1 sideroflexin 1 1.262718 0.02940824 SEC23A Sec23 homolog A (S. cerevisiae) 1.166758 0.0064721 v-crk sarcoma virus CT10 oncogene CRKL homolog (avian)-like 1.22546 0.02004339 IMP (inosine 5'-monophosphate) IMPDH2 dehydrogenase 2 1.186305 0.02984448 SIN3 homolog B, transcription regulator SIN3B (yeast) 1.247232 0.0053172 INHBB inhibin, bet B 1.238504 0.00822597 translocase of inner mitochondrial membrane TIMM8A 8 homolog A (yeast) 1.154276 0.01892605 THOC4 THO complex 4 1.216787 0.0403008 ACINI apoptotic chromatin condensation inducer 1 1.201026 0.02887224

Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value CHMP7 CHMP family, member 7 3.295925 0.04618667 INADL InaD-like (Drosophila) 2.899368 0.00507621 ERRFIl ERBB receptor feedback inhibitor 1 2.848611 0.03785734 MED 12 mediator complex subunit 12 1.963442 0.04534554 DDHD2 DDHD domain containing 2 2.735836 0.04539782

1/694375 16 1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value nudix (nucleoside diphosphate linked moiety NUDT9 X)-type motif9 2.735101 0.00850058 DIAPH1 diaphanous homolog 1 (Drosophila) 2.685718 0.03000495 F R Fll receptor 1.585065 0.04318684 ADAR adenosine deaminase, RNA-specific 1.970478 0.02323278 LGALS8 lectin, galactoside-binding, soluble, 8 1.607202 0.03947108 POLR1B polymerase (RNA) I polypeptide B, 128kDa 1.430873 0.01550162 excision repair cross-complementing rodent ERCC5 repair deficiency, complementation group 5 1.324623 0.03590136 IFITM3 #N/A 2.435717 0.04163527 MCRS1 microspherule protein 1 2.42666 0.04946973 ATPase, Na+/K+ transporting, alpha 1 ATP1A1 polypeptide 1.582011 0.01059971 EDF1 #N/A 2.424154 0.04204104 solute carrier family 20 (phosphate transporter), SLC20A1 member 1 1.821633 0.01516049 INVS inversin 2.402863 0.01659962 NICNl nicolin l 2.388529 0.00908688 WDFY2 WD repeat and FYVE domain containing 2 2.369515 0.01867335 GLUL glutamate-ammonia ligase 2.013353 0.01359148 TP53BP1 tumor protein p53 binding protein 1 1.653193 0.03890936 TSPAN31 tetraspanin 3 1 1.998064 0.04403488 TTC4 tetratricopeptide repeat domain 4 2.305393 0.01 134933 ELOVL family member 6, elongation of long chain fatty acids (FENl/Elo2, SUR4/Elo3-like, ELOVL6 yeast) 2.298864 0.02905437 OSBPL1A oxysterol binding protein-like 1A 2.28078 0.03304009 solute carrier family 4, sodium bicarbonate SLC4A7 cotransporter, member 7 2.276701 0.00738148 HINT2 histidine triad nucleotide binding protein 2 2.272342 0.02016666 PDE8A phosphodiesterase 8A 1.960537 0.01873747 PRUNE prune homolog (Drosophila) 2.261951 0.04105039 CRTAP cartilage associated protein 1.194501 0.01415943 ATP-binding cassette, sub-family G (WHITE), ABCG2 member 2 2.258303 0.02678408 COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.921458 0.01957612 DCTN1 dynactin l (pi 50, glued homolog, Drosophila) 2.247297 0.0361356 RDHl 1 retinol dehydrogenase 11 (all-trans/9-cis/l 1-cis) 1.594865 0.03426753 cyclin-dependent kinase inhibitor 1A (p21, CDKN1A Cipl) 2.238879 0.01566499 LSG1 large subunit GTPase 1 homolog (S. cerevisiae) 2.107797 0.03808136 IFIH1 interferon induced with helicase C domain 1 1.824823 0.04845467 SRPK2 SFRS protein kinase 2 1.531659 0.03108475 GTF2IRD2 GTF2I repeat domain containing 2 1.614706 0.0087574 HDLBP high density lipoprotein binding protein 1.370587 0.02901277 phosphoinositide-3 -kinase, regulatory subunit 1 PIK3R1 (alpha) 1.724967 0.04257376 SEC14L2 SEC14-like 2 (S. cerevisiae) 2.197791 0.02157167 HTRA2 HtrA serine peptidase 2 1.842614 0.04774984 D / 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value FBXW11 F-box and WD repeat domain containing 11 2.088765 0.00313297 ANKRD17 ankyrin repeat domain 1 1.43046 0.04827993 TCEA2 transcription elongation factor A (SII), 2 2.187952 0.04357233 FBXL3 F-box and leucine-rich repeat protein 3 2.176911 0.01974647 O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N- acetylglucosamine:polypeptide-N- OGT acetylglucosaminyl transferase) 1.728718 0.04340233 MYCBP2 MYC binding protein 2 2.168534 0.02526474 IRF7 interferon regulatory factor 7 2.163552 0.01010416 NAV2 neuron navigator 2 1.835983 0.04928384 MACF1 microtubule-actin crosslinking factor 1 2.062381 0.03102047 ashl (absent, small, or homeotic)-like ASH1L (Drosophila) 1.331452 0.03902654 RBBP6 retinoblastoma binding protein 6 1.479665 0.04940251 chaperonin containing TCP1, subunit 3 CCT3 (gamma) 2.143663 0.03791006 UBAP2L ubiquitin associated protein 2-like 1.205878 0.04256504 NDRG2 NDRG family member 2 1.640909 0.03953699 METTL3 methyltransferase like 3 1.487554 0.03923316 TATA box binding protein (TBP)-associated TAFIA factor, RNA polymerase I, A, 48kDa 2.123803 0.01221043 LATS, large tumor suppressor, homolog 2 LATS2 (Drosophila) 2.119657 0.02938295 ST7 suppression of tumorigenicity 7 1.530312 0.02388241 poly(A)-specific ribonuclease (deadenylation PARN nuclease) 2.111073 0.03680447 PLK2 polo-like kinase 2 (Drosophila) 1.89847 0.02392197 SPG20 spastic paraplegia 20 (Troyer syndrome) 2.103392 0.00306415 MPDU1 mannose-P-dolichol utilization defect 1 2.102917 0.01760447 PHF23 #N/A 2.10236 0.00738597 POM121 POM121 membrane glycoprotein (rat) 1.25332 0.04289457 HSPC159 galectin-related protein 1.276374 0.0439434 DnaJ (Hsp40) homolog, subfamily B, member DNAJB6 6 2.086418 0.03741646 ZNF638 zinc finger protein 638 2.082689 0.00361861 phosphatidylinositol transfer protein, PITPNM1 membrane-associated 1 2.08004 0.02403844 DNA cross-link repair 1A (PS02 homolog, S. DCLRE1A cerevisiae) 2.070302 0.00827517 low density lipoprotein receptor-related protein LRP10 10 2.065981 0.04553922 ULK1 unc-51-like kinase 1 (C. elegans) 1.376606 0.04913687 TNRC6A trinucleotide repeat containing 6A 1.452047 0.02369483 PPAP2A phosphatidic acid phosphatase type 2A 1.582666 0.00144035 TTC17 tetratricopeptide repeat domain 1 1.672722 0.02732361 RREBl ras responsive element binding protein 1 1.462738 0.0215814 polymerase (RNA) III (DNA directed) POLR3A polypeptide A, 155kDa 2.037793 0.04734161 DB1/ 694375I6.I Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value DDIT3 DNA-damage-inducible transcript 3 2.035672 0.01260509 DDX51 DEAD (Asp-Glu-Ala-Asp) box polypeptide 51 1.548135 0.04765583 FASN fatty acid synthase 1.948427 0.02462526 C2or£28 chromosome 2 open reading frame 28 1.474813 0.01733917 mitogen-activated protein kinase kinase kinase MAP4K4 kinase 4 1.712186 0.04245277 PEX19 peroxisomal biogenesis factor 19 2.008181 0.00973182 BET1L #N/A 2.00183 0.04957609 diacylglycerol O-acyltransferase homolog 1 DGAT1 (mouse) 1.749071 0.03456439 TK2 thymidine kinase 2, mitochondrial 1.60101 0.04195181 SMYD2 SET and MYND domain containing 2 1.552349 0.04941773 TRAFD1 TRAF-type zinc finger domain containing 1 1.941885 0.02871056 v-erb-b2 erythroblastic leukemia viral oncogene ERJBB3 homolog 3 (avian) 1.981818 0.04875523 ectonucleotide ENPP1 pyrophosphatase/phosphodiesterase 1 1.981336 0.01844171 STX12 syntaxin 12 1.977998 0.03106077 SHROOM3 shroom family member 3 1.977414 0.01628976 PGM2 Phosphoglucomutase 2 1.781686 0.02399861 ZMYM4 zinc finger, MYM-type 4 1.432183 0.03154925 TSC22D1 TSC22 domain family, member 1 1.152544 0.04055428 LDB1 LIM domain binding 1 1.768377 0.04418318 TMEM70 transmembrane protein 70 1.950205 0.02384912 BCL2L11 BCL2-like 1 (apoptosis facilitator) 1.943373 0.01340632 RAS p21 protein activator (GTPase activating RASA1 protein) 1 1.943062 0.01887466 LIMA1 LIM domain and actin binding 1 1.941669 0.04567907 EIF2C2 eukaryotic translation initiation factor 2C, 2 1.737381 0.02796271 PRP39 pre-mRNA processing factor 39 PRPF39 homolog (S. cerevisiae) 1.263236 0.03313913 BAT3 HLA-B associated transcript 3 1.612256 0.02485149 glycerol-3 -phosphate dehydrogenase 2 GPD2 (mitochondrial) 1.923915 0.02166602 IL11RA interleukin 11 receptor, alpha 1.919985 0.01904984 WNK1 WNK lysine deficient protein kinase 1 1.589806 0.03200462 ASXL1 additional sex combs like 1 (Drosophila) 1.470256 0.00998521 BMP2K BMP2 inducible kinase 1.386192 0.04872796 PIAS3 protein inhibitor of activated STAT, 3 1.912841 0.01839942 histidyl-tRNA synthetase 2, mitochondrial HARS2 (putative) 1.715719 0.03591061 transducin-like enhancer of split 1 (E(s l ) TLE1 homolog, Drosophila) 1.9081 8 0.04074464 amyloid beta (A4) precursor protein-binding, APBB2 family B, member 2 1.90255 0.03919277 GSTA4 glutathione S-transferase alpha 4 1.753107 0.00541283 MYBBP1A MYB binding protein (PI 60) l 1.897963 0.01696392 PHF12 #N/A 1.896855 0.04395523 SCAMPI secretory carrier membrane protein 1 1.57467 0.02157253 D l/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value RPL22 ribosomal protein L22 0.00202954 VLDLR very low density lipoprotein receptor 0.02591 145 RTTN rotatin 0.04473924 REPS1 RALBP1 associated Eps domain containing 1 0.03344135 ATP-binding cassette, sub-family G (WHITE), ABCG1 member 1 0.03561249 fasciculation and elongation protein zeta 2 FEZ2 (zygin II) 0.01625731 solute carrier family 1 (folate transporter), SLC19A1 member 1 0.01485065 MFN1 mitofusin 1 0.0499737 BMP7 #N/A 0.04358522 SH3RF1 SH3 domain containing ring finger 1 0.00683851 ACVR2A activin A receptor, type IIA 0.04361939 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, SMARCA2 member 2 0.01914396 ITGB4 integrin, beta 4 0.04837165 MTMR1 myotubularin related protein 1 0.01841331 potassium large conductance calcium-activated KCNMA1 channel, subfamily M, alpha member 1 0.02490189 ELL2 elongation factor, RNA polymerase II, 2 0.02073358 MAPK12 mitogen-activated protein kinase 1 0.02403095 SEC23A Sec23 homolog A (S. cerevisiae) 0.02654777 EPC1 enhancer of polycomb homolog 1 (Drosophila) 0.03620974 SSBP4 single stranded DNA binding protein 4 0.0091075 ZNF692 zinc finger protein 692 0.04823366 FOXP1 forkhead box PI 0.01077085 Smg-5 homolog, nonsense mediated mRNA SMG5 decay factor (C. elegans) 0.01248203 ASNS asparagine synthetase (glutamine-hydrolyzing) 0.04490557 minichromosome maintenance complex MCM3AP component 3 associated protein 0.01036449 NUMA1 nuclear mitotic apparatus protein 1 0.02466567 NELF nasal embryonic LHRH factor 0.04955878 RPP14 ribonuclease P/MRP 14kDa subunit 0.04069763 PDK1 pyruvate dehydrogenase kinase, isozyme 1 0.03042126 TPP2 tripeptidyl peptidase II 0.02199587 cytoplasmic polyadenylation element binding CPEB2 protein 2 0.00139721 ARIH2 ariadne homolog 2 (Drosophila) 0.04036547 erythrocyte membrane protein band 4.1 EPB41 (elliptocytosis l , RH-linked) 0.02384749 ITSN1 intersectin 1 (SH3 domain protein) 0.0462667 LAPTM4B lysosomal protein transmembrane 4 beta 0.01663365 SMAD6 SMAD family member 6 0.04895342 CREM cAMP responsive element modulator 0.01481585 SERTAD1 #N/A 0.03107296 MRPS25 Mitochondrial ribosomal protein S25 0.01791241 1/6943 7516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value metal response element binding transcription MTF2 factor 2 1.431461 0.04435086 SHKBP1 SH3KBP1 binding protein 1 1.789197 0.01337287 PPIL2 peptidylprolyl isomerase (cyclophilin)-like 2 1.619019 0.03839263 adaptor-related protein complex 1, beta 1 AP1B1 subunit 1.779553 0.01993621 C9orf72 chromosome 9 open reading frame 72 1.779325 0.00116813 WD repeat domain, phosphoinositide WIPI2 interacting 2 1.777875 0.04845168 DGCR2 DiGeorge syndrome critical region gene 2 1.777194 0.03677183 ELL elongation factor RNA polymerase II 1.775647 0.02696673 TNIP1 TNFAIP3 interacting protein 1 1.362235 0.02962173 LASS2 LAG1 homolog, ceramide synthase 2 1.383183 0.01736726 MAP2K3 mitogen-activated protein kinase kinase 3 1.252382 0.01292775 UBL4A #N/A 1.766604 0.01994057 FOXK2 forkhead box K2 1.483924 0.0323877 nuclear factor of kappa light polypeptide gene NFKB1 enhancer in B-cells 1 1.466917 0.00255794 ATF3 activating transcription factor 3 1.756661 0.0451451 CEP350 centrosomal protein 350kDa 1.351 128 0.03670049 HDDC2 HD domain containing 2 1.153537 0.00641685 sphingomyelin phosphodiesterase 2, neutral SMPD2 membrane (neutral sphingomyelinase) 1.505414 0.04020793 IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 1.642147 0.03956772 GAB1 GRB2-associated binding protein 1 1.746467 0.03029872 ERF #N/A 1.74482 0.02510774 RYK RYK receptor-like tyrosine kinase 1.461366 0.03625633 STK11IP serine/threonine kinase 11 interacting protein 1.736757 0.02103678 BCL2L13 BCL2-like 13 (apoptosis facilitator) 1.429059 0.02860466 ZBTB2 zinc finger and BTB domain containing 2 1.733558 0.02724021 RAB3IP RAB3A interacting protein (rabin3) 1.73291 0.03062512 GALT galactose- -phosphate uridylyltransferase 1.397966 0.00247261 SELENBP1 selenium binding protein 1 1.548317 0.01943454 Rho guanine nucleotide exchange factor (GEF) ARHGEF3 3 1.729836 0.04145086 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated MLLT10 to, 10 1.546189 0.01475505 ariadne homolog, ubiquitin-conjugating enzyme ARIH1 E2 binding protein, 1 (Drosophila) 1.446394 0.0394967 IRF6 interferon regulatory factor 6 1.7131 18 0.0205667 CREG1 cellular repressor of ElA-stimulated genes 1 1.310534 0.02867724 mitogen-activated protein kinase kinase kinase MAP4K3 kinase 3 1.710348 0.0179431 1 ZFR zinc finger RNA binding protein 1.656317 0.01 174294 LysM, putative peptidoglycan-binding, domain LYSMD2 containing 2 1.589339 0.02093268 LPIN2 lipin 2 1.708429 0.00705372 TFB2M transcription factor B2, mitochondrial 1.414276 0.00766602 >B1/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value FXYD domain containing ion transport FXYD5 regulator 5 1.701 181 0.0201854 FNBP4 formin binding protein 4 1.349354 0.00845931 BTB and CNC homology 1, basic leucine BACH1 zipper transcription factor 1 1.696301 0.02582705 transmembrane emp24 protein transport domain TMED4 containing 4 1.694517 0.0165239 retinol saturase (all-trans-retinol 13,14- RETSAT reductase) 1.692359 0.0411033 GAS8 growth arrest-specific 8 1.55427 0.0138367 IDH3A isocitrate dehydrogenase 3 (NAD+) alpha 1.683264 0.04905133 TES testis derived transcript (3 LIM domains) 1.542686 0.0424636 EZH1 enhancer of zeste homolog 1 (Drosophila) 1.569122 0.03681327 PXN paxillin 1.283966 0.048801 14 TWSG1 Twisted gastrulation homolog 1 (Drosophila) 1.590384 0.03366619 PPP1R15A #N/A 1.666918 0.00530079 PDCD2 programmed cell death 2 1.664955 0.02292029 MTMR10 myotubularin related protein 10 1.594912 0.01 191 GPR133 G protein-coupled receptor 133 1.349679 0.02919616 CASP3 caspase 3, apoptosis-related cysteine peptidase 1.275471 0.00672259 succinate-CoA ligase, GDP-forming, beta SUCLG2 subunit 1.61146 0.01434601 PITX2 #N/A 1.38095 0.03603224 RNASEH1 ribonuclease HI 1.22204 0.020311 13 PELI1 pellino homolog 1 (Drosophila) 1.47698 0.03398163 EFNA1 #N/A 1.641752 0.02231982 JUP junction plakoglobin 1.639367 0.03601004 phosphoinositide-3-kinase, regulatory subunit 2 PIK3R2 (beta) 1.6247 0.04549777 USP38 ubiquitin specific peptidase 38 1.328488 0.03761775 TBRG4 #N/A 1.40939 0.02950791 N4BP1 NEDD4 binding protein 1 1.180702 0.04692864 ZFP28 zinc finger protein 28 homolog (mouse) 1.270796 0.03986652 PDCD6IP programmed cell death 6 interacting protein 1.341445 0.02712429 TSN translin 1.399509 0.03659249 ZMYM6 zinc finger, MYM-type 6 1.607937 0.03222668 tissue factor pathway inhibitor (lipoprotein- TFPI associated coagulation inhibitor) 1.170572 0.03900407 RIT1 Ras-like without CAAX 1 1.493381 0.00705308 ZFP30 #N/A 1.606079 0.04811928 JUN jun oncogene 1.60477 0.01920584 E2F5 E2F transcription factor 5, pl30-binding 1.574504 0.04111575 SMYD1 #N/A 1.602613 0.03160765 GFPT2 glutamine-fructose-6-phosphate transaminase 2 1.601761 0.00786173 solute carrier family 1 (glutamate/neutral amino SLC1A4 acid transporter), member 4 1.6011 11 0.017141 16 MAPK8 mitogen-activated protein kinase 8 1.352867 0.03733872 LM02 #N/A 1.585683 0.01 178633 IKBKE inhibitor of kappa light polypeptide gene 1.585318 0.02560331 DBl/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value enhancer in B-cells, kinase epsilon polycystic kidney disease 2 (autosomal PKD2 dominant) 1.355906 0.03251514 RASA3 RAS p21 protein activator 3 1.580655 0.03063955 ZNF703 zinc finger protein 703 1.553516 0.0157481 SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.374893 0.04735748 DAB2IP DAB2 interacting protein 1.325257 0.04430944 MFHAS1 #N/A 1.429933 0.04621658 ubiquitin specific peptidase 7 (herpes virus- USP7 associated) 1.2173 0.03971564 solute carrier family 12 (sodium/potassium/chloride transporters), SLC12A2 member 2 1.379717 0.01203849 TEC Tec protein tyrosine kinase 1.561419 0.04835099 lymphotoxin beta receptor (TNFR superfamily, LTBR member 3) 1.56131 0.01734089 CD83 CD83 molecule 1.393225 0.03750887 BAIAP2 BAI1-associated protein 2 1.558511 0.02805553 mutS homolog 2, colon cancer, nonpolyposis MSH2 type 1 (E. coli) 1.301052 0.00303927 ALDH7A1 aldehyde dehydrogenase 7 family, member A l 1.521211 0.04933379 COX17 cytochrome c oxidase assembly COX17 homolog (S. cerevisiae) 1.548985 0.00063577 proteasome (prosome, macropain) 26S subunit, PSMD12 non-ATPase, 2 1.54839 0.03297181 DYNC1I1 dynein, cytoplasmic 1, intermediate chain 1 1.547255 0.0015712 COL4A1 collagen, type IV, alpha 1 1.340948 0.04402007 protein tyrosine phosphatase, non-receptor type PTP 18 18 (brain-derived) 1.5449 0.04522658 PPFIBP2 #N/A 1.513922 0.01840277 RBPMS RNA binding protein with multiple splicing 1.422673 0.041 19182 ANKRD28 ankyrin repeat domain 28 1.522866 0.0295649 C10orf58 #N/A 1.392475 0.0313261 WDR13 WD repeat domain 13 1.53985 0.02618777 ATP-binding cassette, sub-family A (ABC1), ABCA1 member 1 1.53626 0.0201419 dolichyl-phosphate mannosyltransferase DPM2 polypeptide 2, regulatory subunit 1.42053 0.00599389 PHKG2 phosphorylase kinase, gamma 2 (testis) 1.532241 0.03755378 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated MLLT3 to, 3 1.336207 0.0340955 GALC #N/A 1.337734 0.04874618 FLT3LG fms-related tyrosine kinase 3 ligand 1.524077 0.01175394 ZNF436 zinc finger protein 436 1.523707 0.04067693 HDAC5 histone deacetylase 5 1.313934 0.0481495 IFNGR1 interferon gamma receptor 1 1.485695 0.03541863 SRRM1 serine/arginine repetitive matrix 1 1.449417 0.01719139 RABEP1 rabaptin, RAB GTPase binding effector protein 1.202797 0.0453199 DBl/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells Gene Fold Ttest Symbol Gene Description Change P value 1 BMP1 bone morphogenetic protein 1 1.32758 0.03343608 MCOLN2 mucolipin 2 1.51452 0.04997968 EFNB2 ephrin-B2 1.511313 0.02811974 interleukin 16 (lymphocyte chemoattractant IL16 factor) 1.499957 3.09E-06 FAM91A1 family with sequence similarity 91, member A l 1.407477 0.01878871 WD 78 WD repeat domain 78 1.499613 0.03715928 TRAF family member-associated NFKB TANK activator 1.24674 0.02488358 KIFAP3 kinesin-associated protein 3 1.458765 0.04901628 LARS Leucyl-tRNA synthetase 1.46382 0.0271 1871 PGCP plasma glutamate carboxypeptidase 1.485871 0.00774448 VAMP5 #N/A 1.48482 0.02867714 LDHB lactate dehydrogenase B 1.484571 0.01769543 cytochrome P450, family 51, subfamily A, CYP51A1 polypeptide 1 1.483035 0.00605888 NCKAPl NCK-associated protein 1 1.3721 16 0.02620886 TCF15 transcription factor 5 (basic helix-loop-helix) 1.474894 0.00719009 KRT7 keratin 7 1.345142 0.04343201 FBX09 F-box protein 9 1.276761 0.02422462 solute carrier family 4, anion exchanger, SLC4A3 member 3 1.472698 0.01015349 SYTL4 synaptotagmin-like 4 1.427768 0.0322787 ZNF213 zinc finger protein 2 3 1.463007 0.01 143018 nuclear factor I X (CCAAT-binding NFIX transcription factor) 1.458648 0.02610177 ZNF622 zinc finger protein 622 1.305364 0.03391459 GAA glucosidase, alpha; acid 1.390145 0.02416388 UBC #N/A 1.39239 0.04488279 NKIRAS1 NFKB inhibitor interacting Ras-like 1 1.434868 0.04111426 IL4R interleukin 4 receptor 1.367682 0.04745193 PYCRL pyrroline-5-carboxylate reductase-like 1.383376 0.02332003 protein tyrosine phosphatase, non-receptor type PTP 12 12 1.407633 0.04343223 CD34 CD34 molecule 1.406256 0.02143454 IFRD1 interferon-related developmental regulator 1 1.223621 0.0461768 transcription elongation factor B (SIII), TCEB3 polypeptide 3 ( 1lOkDa, elongin A) 1.403204 0.03240308 EPRS glutamyl-prolyl-tRNA synthetase 1.308599 0.02361163 ATP5D #N/A 1.386046 0.03800337 AEBP2 AE binding protein 2 1.362569 0.03985048 ZFX #N/A 1.254057 0.02842691 BCL3 B-cell CLL/lymphoma 3 1.338873 0.03515185 MRPL3 mitochondrial ribosomal protein L3 1.321518 0.01629641 mitogen-activated protein kinase kinase kinase MAP3K11 11 1.262091 0.02976909 eukaryotic translation initiation factor 4E EIF4EBP1 binding protein 1 1.242901 0.03329666 1/ 69437516.1 Supplemental Table 6. Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Multiple Myeloma (MM) Signature. Only in Fold Ttest Lactate Gene Description Change P value glycine cleavage system protein H GCSH (aminomethyl carrier) 6.024608 0.04401522 ASF1 anti-silencing function 1 homolog A (S. ASF1A cerevisiae) 4.469944 0.01353041 signal transducing adaptor molecule (SH3 STAM2 domain and ITAM motif) 2 4.170061 0.00948584 MINA MYC induced nuclear antigen 4.035887 0.00750673 DBF4 DBF4 homolog (S. cerevisiae) 3.845044 0.01450426 chaperonin containing TCP1, subunit 5 CCT5 (epsilon) 2.739476 0.00602847 DMXL1 Dmx-like 1 3.07451 1 0.00708549 KRIT1 KR T , ankyrin repeat containing 2.533715 0.00341833 EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242 DDX18 DEAD (Asp-Glu- Ala-Asp) box polypeptide 18 2.65979 0.04995911 DnaJ (Hsp40) homolog, subfamily B, member DNAJB14 14 2.625377 0.00031245 Split hand/foot malformation (ectrodactyly) SHFM1 type 1 2.41 1671 0.02417581 C7orf30 chromosome 7 open reading frame 30 2.375592 0.00732418 protein phosphatase 1, regulatory (inhibitor) PPP1R12A subunit 12A 2.277063 0.04329455 protein kinase, DNA-activated, catalytic PRKDC polypeptide 1.496476 0.04042323 IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745 LRRC40 leucine rich repeat containing 40 2.063667 0.0216401 SLC25A36 solute carrier family 25, member 36 2.031104 0.01642812 nuclear autoantigenic sperm protein (histone- NASP binding) 1.586624 0.02198518 telomeric repeat binding factor (NIMA- TERF1 interacting) 1 1.863569 0.01246509 UPF3 regulator of nonsense transcripts UPF3A homolog A (yeast) 1.23028 0.0287505 intraflagellar transport 57 homolog IFT57 (Chlamydomonas) 1.410484 0.02169174 intraflagellar transport 74 homolog IFT74 (Chlamydomonas) 1.369324 0.01094548 LEMD3 LEM domain containing 3 1.44673 0.04092375 fibroblast growth factor (acidic) intracellular FIBP binding protein 1.599584 0.00865392 LAP3 leucine aminopeptidase 3 1.260347 0.04343932 DHX29 DEAH (Asp-Glu-Ala-His) box polypeptide 29 1.4701 13 0.01019979 ABHD3 abhydrolase domain containing 3 1.547037 0.04585433 GEMIN5 gem (nuclear organelle) associated protein 5 1.439594 0.0397608 elongation factor Tu GTP binding domain EFTUD2 containing 2 1.454941 0.01886939 C15orf41 chromosome 15 open reading frame 4 1 1.442137 0.04387507 ERCC1 excision repair cross-complementing rodent 1.265089 0.04242011 D / 69437516.1 Supplemental Table 6. Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Multiple Myeloma (MM) Signature. On y in Fold Ttest Lactate Gene Description Change P value repair deficiency, complementation group 1 (includes overlapping antisense sequence) PAK1IP1 PAK1 interacting protein 1 1.26866 0.0392548 SNX19 Sorting nexin 19 1.382253 0.03833771 ILF3 interleukin enhancer binding factor 3, 90kDa 1.243423 0.02255549 translocase of inner mitochondrial membrane TIMM50 50 homolog (S. cerevisiae) 1.300325 4.55E-05 TRIB1 tribbles homolog 1 (Drosophila) 1.184163 0.02736849

Supplemental Table 7: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Hepatocellular Carcinoma (HCC) Signature Only in Fo d Ttest P Lactate Gene Description Change value CD2AP CD2-associated protein 2.509456 0.04171078 RPS3A ribosomal protein S3A 4.603982 0.03886604 CCT6A chaperonin containing TCP1, subunit 6A (zeta 1) 2.226682 0.02645749 CENPF centromere protein F, 350/400ka (mitosin) 3.299657 0.01890505 ZNF 138 zinc finger protein 138 3.162613 0.04255118 CCT5 chaperonin containing TCP1, subunit 5 (epsilon) 2.739476 0.00602847 HDAC2 histone deacetylase 2 1.713956 0.04708192 ANLN anillin, actin binding protein 3.097471 0.03519748 HMGB2 high-mobility group box 2 1.972844 0.03882638 RWDD1 RWD domain containing 1 2.70643 0.03976333 ACTR3 ARP3 actin-related protein 3 homolog (yeast) 2.500061 0.02540777 nucleophosmin (nucleolar phosphoprotein B23, NPM1 numatrin) 2.406641 0.01665033 EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 2.394143 0.01844291 RPL9 ribosomal protein L9 1.678778 0.02683837 USP1 ubiquitin specific peptidase 1 2.204293 0.02425862 hypoxia inducible factor 1, alpha subunit (basic helix- HIF A loop-helix transcription factor) 1.591415 0.00884964 tyrosine 3-monooxygenase/tryptophan 5- YWHAQ monooxygenase activation protein, theta polypeptide 2.122941 0.02980982 PCNA proliferating cell nuclear antigen 1.306526 0.02897492 RPL 12 ribosomal protein L12 1.645702 0.03148393 NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931 RPE ribulose-5-phosphate-3-epimerase 1.72725 0.04901899 ECT2 epithelial cell transforming sequence 2 oncogene 1.412257 0.00609004 UBA2 ubiquitin-like modifier activating enzyme 2 1.536631 0.03719408 NFE2L3 nuclear factor (erythroid-derived 2)-like 3 1.738235 0.01922635 KNTC1 kinetochore associated 1 1.573628 0.03209189 LAMB 1 laminin, beta 1 1.484995 0.00653142 SLC34A1 solute carrier family 34 (sodium phosphate), member 1 1.357953 0.01540008 KLF5 Kruppel-like factor 5 (intestinal) 1.349817 0.03913202 ROD1 ROD1 regulator of differentiation 1 (S. pombe) 1.200754 0.0474292 serpin peptidase inhibitor, clade H (heat shock protein SERPINH1 47), member 1, (collagen binding protein 1) 1.32396 0.01919945

DBl/ 69437516.1 Supplemental Table 7: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Hepatocellular Carcinoma (HCC) Signature Only in Fold Ttest P Lactate Gene Description Change value UDP-GlcNAc:betaGal beta-l,3-N- B3GNT5 acetylglucosaminyltransferase 5 1.200695 0.01960692

DB1/ 694375I6.1 CLAIMS

1. A method for identifying a mammalian cell as neoplastic, the method comprising detecting in a test mammalian cell (e.g. breast cancer cell) a level of gene expression pattern or activity,

wherein the level of gene expression pattern or activity is induced by a set of at least one high-energy metabolite (e.g., ketones or lactate or acetoacetate or oxaloacetate or citrate or a- ketoglutarate or glutamine); and

identifying the test mammalian cell as neoplastic when a difference between the level of gene expression pattern or activity in the test mammalian cell and a corresponding level of gene expression pattern or activity in a control mammalian cell is detected.

2. A method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which inhibits metabolite-induced gene expression pattern or activity of a set of genes, the method comprising (a) subjecting an in vitro cell culture of cancer cells to treatment with a set of at least one or more metabolites to induce gene expression pattern or activity of a set of genes, wherein the set of genes is selected from at least one table from the group consisting of Tables 1-7; (b) thereafter treating the cell culture with the therapeutic agent; and (c) comparing the level of gene expression pattern or activity caused by the set of at least one or more metabolites, wherein a corresponding gene expression pattern or activity in a control cancer cell culture not treated with the set of the set at least one or more metabolites, wherein a difference in the level of gene expression pattern or active is indicative of the ability of the therapeutic agent to treat cancer in the cancer patient.

3. A method for evaluating gene expression in cancer cells, the method comprising treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as glutamine, acetoacetate, lactate or 3-hydroxybutyrate); and assessing changes in gene expression resulting from the treatment with said set of at least one metabolite; wherein said method comprises generating labeled polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

4. A method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one or more metabolites, the method comprising: (a) subjecting an in vitro cancer cell culture to treatment with the set of at least one or more metabolites; (b) DBl/ 69437516.1 thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture, wherein the control cell had not been treated with the at least one or more metabolites; whereby a difference between the level of gene expression in the in vitro cancer cell culture and the level of gene expression in the control cell culture is an indication that the gene expression pattern of the set of at least one cancer associated gene is induced by the set of at least one or more metabolites; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

5. A method for predicting a clinical outcome in a cancer patient, comprising (a) subjecting a first in vitro culture of cancer cells derived from a sample obtained from a cancer patient to treatment with a set of at least one or more metabolites; and (b) assessing a level of gene expression pattern in the first in vitro culture of cancer cells; and (c) comparing the level of gene expression pattern of the first in vitro cancer cell culture with a corresponding level of gene expression pattern in a second in vitro cancer cell culture (control sample) also derived from a sample obtained from the cancer patient, whereby a difference between the level of the gene expression pattern in the first in vitro cancer cell culture and the level of gene expression pattern in the second in vitro cancer cell culture is indicative of the clinical outcome (e.g., high risk of cancer recurrence, or high risk of cancer metastasis, and decreased overall survival).

6. The method of claim 5, wherein the clinical outcome predicts prognosis for survival.

7. The method of claim 5, wherein the clinical outcome is a poor clinical outcome (e.g., shorter survival or shorter overall survival).

8. The method of claim 5, wherein the clinical outcome is selected from the group consisting of recurrence of cancer, increased survival of cancer, shorter survival of cancer, and cancer progression in the cancer patient.

9. The method of claim 5, wherein the clinical outcome is selected from the group consisting of decreased overall survival of cancer and/or increased likelihood of cancer progression in the cancer patient.

10. A method of stratifying a subject or a group of subjects having a cancer for a clinical trial, the method comprising: (a) treating an in vitro culture of cancer cells derived from a biological DBl/ 69437516.1 sample obtained from the subject or each member of the group of subjects having the cancer with a set of at least one or more metabolites (such as 3-hydroxybutyrate, lactate, glutamine and acetoacetate); (b) assessing changes in gene expression induced by said set of at least one or more metabolites; (c) comparing the level of gene expression in the in vitro culture of cancer cells with a level of gene expression in a control cancer cell culture; and (d) stratifying the subject or the group of subjects for the clinical trial on the basis of a difference between the level of gene expression in the in vitro culture of cancer cells and the level of gene expression in the control cancer cell culture.

. A method for culturing stem cells, including mesenchymal stem cells, embryonic stem cells, including human embryonic stem cells, said method comprising growing said stem cells in a culture medium in the presence of at least one or more metabolites (e.g., acetoacetate, 3- hydroxybutyrate, lactate, glutamine).

12. The method of claim 11, further comprising isolating stem cells from the culture medium.

13. A method for discovering a biological marker (biomarker) of a cancer whose growth is modulated by mitochondrial oxidative metabolism, the method comprising:

(a) contacting a set of at least one or more metabolites (e.g., 3-hydroxybutyrate or lactate or acetoacetate or oxaloacetate or citrate or a-ketoglutarate or glutamine or combinations thereof) to a first sample of a cancer cell line, a test cancer cell line;

(b) assessing a level of gene expression pattern in the test cancer cell line; and

(c) comparing the level of gene expression pattern of the test cancer cell line with a level of gene expression pattern in a second sample of the cancer cell line, a control cancer cell line,

whereby a difference between the level of the gene expression pattern in the test cancer cell line and the level of gene expression pattern in the control cancer cell line is a biomarker of mitochondrial oxidative metabolism in the cancer represented by the cancer cell.

14. A biomarker discovered according to the method of claim 13.

1 . A method for predicting a clinical outcome in a cancer patient, comprising:

(a) subjecting a first sample of cancer cell line corresponding to the same type of cancer in the cancer patient to treatment with a set of at least one or more metabolites;

(b) assessing a level of gene expression pattern in the first sample of cancer cell line; and DBl/69437516.1 (c) comparing the level of gene expression pattern of the first sample cancer cell line with a level of gene expression pattern in a second sample of the cancer cell line not treated with the at least one or more metabolites, whereby a difference between the level of the gene expression pattern in the first sample of cancer cell line and the level of gene expression pattern in the second sample of the cancer cell line is indicative of the clinical outcome (e.g., high risk of cancer recurrence and/or high risk of cancer metastasis and/or decreased overall survival).

16. A method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which prevents or inhibits metabolite-induced gene expression pattern or activity in a sample of cancer cell line corresponding to the same type of cancer in the cancer patient, the method comprising (a) subjecting a first sample of cancer cell line and a second sample of the cancer cell line to treatment with a set of at least one or more metabolites to induce gene expression pattern or activity of a set of genes in the first and second samples of the cancer cell line; (b) thereafter treating the first sample of the cancer cell line with a test therapeutic agent; and (c) comparing the level of gene expression pattern or activity caused by the set of at least one or more metabolites in the first sample of cancer cell line with the level of gene expression pattern or activity in the second sample of the cancer cell line, wherein a difference in the level of gene expression pattern or active is indicative of the ability of the test therapeutic agent to treat cancer in the cancer patient.

DB l 69437516.1