DOCSLIB.ORG

Platelet Isoform of Phosphofructokinase Promotes Aerobic Glycolysis and the Progression of Non‑Small Cell Lung Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Platelet Isoform of Phosphofructokinase Promotes Aerobic Glycolysis and the Progression of Non‑Small Cell Lung Cancer MOLECULAR MEDICINE REPORTS 23: 74, 2021 Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer FUAN WANG1, LING LI2 and ZHEN ZHANG3 1Department of Surgical Group, Medical College of Pingdingshan University, Pingdingshan, Henan 467000; 2Department of Respiratory Medicine, First People's Hospital of Jinan, Jinan, Shandong 250000; 3Department of Neurosurgery, Shandong Provincial Hospital, Jinan, Shandong 250012, P.R. China Received April 2, 2020; Accepted October 19, 2020 DOI: 10.3892/mmr.2020.11712 Abstract. The platelet isoform of phosphofructokinase by western blotting. Glucose uptake, lactate production and (PFKP) is a rate‑limiting enzyme involved in glycolysis that the adenosine trisphosphate/adenosine diphosphate ratio serves an important role in various types of cancer. The aim were measured using the corresponding kits. The results of of the present study was to explore the specific regulatory the present study demonstrated that PFKP expression was relationship between PFKP and non‑small cell lung cancer upregulated in NSCLC tissues and cells, and PFKP expression (NSCLC) progression. PFKP expression in NSCLC tissues was related to lymph node metastasis and histological grade. and corresponding adjacent tissues was detected using In addition, overexpression of PFKP inhibited cell apoptosis, reverse transcription‑quantitative polymerase chain reac‑ and promoted proliferation, migration, invasion and glycolysis tion (RT‑qPCR) and immunohistochemical analysis. PFKP of H1299 cells, whereas knockdown of PFKP had the opposite expression in human bronchial epithelial cells (16HBE) and effects. In conclusion, PFKP inhibited cell apoptosis, and NSCLC cells (H1299, H23 and A549) was also detected using promoted proliferation, migration, invasion and glycolysis of RT‑qPCR. Cell proliferation was detected by Cell Counting NSCLC cells; these findings may lay the foundation for novel Kit‑8 and colony formation assays. Transwell invasion and treatments of NSCLC. wound healing assays, and flow cytometry were used to detect cell invasion, migration and apoptosis, respectively. Introduction The expression levels of glycolysis‑associated enzymes (hexokinase‑2, lactate dehydrogenase A and glucose trans‑ Lung cancer is one of the major diseases endangering human porter‑1), epithelial‑mesenchymal transition‑related proteins health worldwide (1). The incidence and mortality rates of (N‑cadherin, vimentin and E‑cadherin) and apoptosis‑related lung cancer are high, particularly non‑small cell lung cancer proteins (caspase‑3 and B‑cell lymphoma‑2) were detected (NSCLC) (2,3). Invasion and metastasis are the main causes of poor prognosis and high mortality rate in patients with lung cancer (4). Although great efforts, such as the identification of novel biomarkers, establishment of modified operations and development of specific drugs, have been made in the clinical Correspondence to: Dr Zhen Zhang, Department of Neurosurgery, Shandong Provincial Hospital, 324 Jingwuwei 7th Road, Jinan, setting, the postoperative survival rate of patients has not Shandong 250012, P.R. China significantly improved (5,6). Therefore, it is of great clinical E‑mail: [email protected] significance to explore the molecular mechanisms underlying the progression of NSCLC. Abbreviations: ADP, adenosine diphosphate; ATP, adenosine Glucose metabolism is one of the most distinguishing triphosphate; BC, breast cancer; Bcl‑2, B‑cell lymphoma‑2; CCK‑8, characteristics between normal and tumorigenic cells (7). Cell Counting Kit‑8; EMT, epithelial‑mesenchymal transition; Tumor cells mainly rely on glycolysis to obtain energy, even in FBS, fetal bovine serum; GBM, glioblastoma; Glut‑1, glucose aerobic environments; this is known as the Warburg effect (8). transporter‑1; HCC, hepatocellular carcinoma; HK‑2, hexokinase‑2; A previous study revealed that the growth and survival of HRP, horseradish peroxidase; IHC, immunohistochemistry; tumor cells depend on the transformation from anaerobic LDHA, lactate dehydrogenase A; NSCLC, non‑small cell lung glycolysis to aerobic glycolysis (9). Aerobic glycolysis provides cancer; OD, optical density; PFK‑1, phosphofructokinase‑1; PFKL, liver isoform of phosphofructokinase; PFKP, platelet isoform of a material basis for the survival, growth and proliferation of phosphofructokinase; PKM2, pyruvate kinase M2; RT‑qPCR, tumor cells (10). Furthermore, a large amount of lactic acid reverse transcription‑quantitative polymerase chain reaction; causes damage to the body, which is conducive to tumor siRNA, small interfering RNA tissues invading adjacent normal tissues (11). In recent years, the Warburg effect has garnered much attention in the study Key words: PFKP, NSCLC, aerobic glycolysis, proliferation, EMT of tumor development mechanisms (12,13). Although the Warburg effect has been recognized in NSCLC (14‑16), the driving mechanism of aerobic glycolysis remains unknown. 2 WANG et al: PFKP PROMOTES PROGRESSION OF NSCLC The platelet isoform of phosphofructokinase (PFKP) is a the slides were incubated with a secondary antibody labeled rate‑limiting enzyme involved in glycolysis, which can cause with horseradish peroxidase (HRP) (1:2,000; cat. nos. ab205719 the conversion of fructose 6‑phosphate to fructose 1,6‑bisphos‑ or ab205718; Abcam) for 30 min at room temperature and phate (17). Enhanced activity of PFKP can increase glycolysis, 3'‑diaminobenzidine reagent (Beijing Solarbio Science & increase fatty acid oxidation, and promote DNA biosynthesis Technology Co., Ltd.) was added to the slides for visualization. and repair, thereby enhancing tumor cell growth, migration Finally, the sections were dehydrated, cleared with xylene and and invasion (18,19). It has been reported that PFKP expres‑ fixed with resin. Two experienced pathologists independently sion is upregulated in various types of cancer, including breast analyzed the IHC results. Brown particles were considered cancer (BC) (20), hepatocellular carcinoma (HCC) (17) and positive expression of PFKP, HK‑2 and PKM2. renal carcinoma (21). However, to the best of our knowledge, the specific regulatory relationship between PFKP and NSCLC Cell culture. Human bronchial epithelial cells (16HBE) and progression remains unclear. NSCLC cells (H1299, H23 and A549) were purchased from The present study aimed to assess the effects of PFKP on American Type Culture Collection. All cells were grown in NSCLC progression, and further investigated the effects of RPMI‑1640 medium (Gibco; Thermo Fisher Scientific, Inc.) PFKP on cell proliferation, apoptosis, migration, invasion and supplemented with 10% fetal bovine serum (FBS; Gibco; glycolysis. The present findings may provide a basis for novel Thermo Fisher Scientific, Inc.) and cultured in an incubator strategies for the treatment of NSCLC. containing 5% CO2 at 37˚C. Materials and methods Cell transfection. H1299 cells were divided into control (without treatment), pVMV6‑ENTRY [negative control (NC); The Cancer Genome Atlas (TCGA) data analysis. The cells were transfected with pCMV6 empty plasmid] and mRNA gene expression data were downloaded from TCGA pVMV6‑PFKP (overexpression of PFKP; cells were trans‑ LUAD datasets (https://portal.gdc.cancer.gov/). Overall fected with pCMV6‑PFKP plasmid) groups. H23 cells were survival information of all TCGA datasets was obtained divided into control (without treatment), small interfering RNA from supplementary data (22). For differentially expressed (siRNA/si)‑NC (NC; cells were transfected with NC siRNAs), gene (DEG) analysis, PFKP mRNA expression in cancer si1‑PFKP (knockdown of PFKP; cells were transfected with tissues and paracancerous (normal) tissues was analyzed si1‑PFKP) and si2‑PFKP (knockdown of PFKP; cells were using the DESeq2 R package (23); the adjusted P‑value for transfected with si2‑PFKP) groups. The plasmids (50 ng) and each gene was calculated using the false‑discovery rate siRNAs (50 nM) were transfected into cells (1x104 cells/well) (FDR) method. The cut‑off to detect DEGs was an FDR of using Lipofectamine® 3000 (Invitrogen; Thermo Fisher <0.05 and an absolute log2‑fold change of >1. For overall Scientific, Inc.) according to the manufacturer's instructions. survival analysis, data analysis was performed in R package The pCMV6‑PFKP, pVMV6‑ENTRY, siRNA and siRNA‑NC ‘survival’ (24) using the Kaplan‑Meier curve method, and a were purchased from OriGene Technologies, Inc. The log‑rank test was used to compare survival times between sequences for the siRNAs were as follows: si‑NC sense, 5'‑GGC two groups. UAC GUC CAG GAG CGC AUU‑3' and antisense, 5'‑UGC GCU CCU GGA CGU AGC CUU‑3'; si1‑PFKP sense, 5'‑GCU CCA Patient and tissue samples. In the present study, NSCLC UUC UUG GGA CAA ATT‑3' and antisense, 5'‑AGA UUC UGG tissues and corresponding adjacent tissues (>2 cm away AAG GAA CAC CTT‑3'; si2‑PFKP sense, 5'‑GGU GUU CCU from the tumor edge) were collected from 84 patients who UCC AGA AUC UTT‑3' and antisense, 5'‑UUU GUC CCA AGA underwent primary surgical resection of NSCLC between AUG GAG CTT‑3'; and PFKP sense, 5'‑GGA CGC GGA CGA January 2018 and December 2019 at Shandong Provincial CTC CCG GGC‑3' and antisense, 5'‑GTC AGA CAC TCC AGG Hospital (Jinan, China). None of the patients received radio‑ GCT GCA CAT GTT CC‑3'. A total of 48 h post‑transfection, therapy or chemotherapy prior to surgical resection, and follow‑up experiments were conducted. the diagnosis of NSCLC was assessed by an experienced pathologist. All tissue samples were
Load more

Recommended publications
  • Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
    Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent
    [Show full text]
  • Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment
    Cancer Microenvironment (2019) 12:149–167 https://doi.org/10.1007/s12307-019-00226-0 REVIEW Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment Mohd Rihan1 & Lakshmi Vineela Nalla1 & Anil Dharavath1 & Amit Shard3 & Kiran Kalia2 & Amit Khairnar1 Received: 18 March 2019 /Accepted: 17 May 2019 /Published online: 10 June 2019 # Springer Nature B.V. 2019 Abstract Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing
    [Show full text]
  • PKM2 Determines Myofiber Hypertrophy in Vitro and Increases
    International Journal of Molecular Sciences Article PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle 1, 2,3, , 4 Sander A. J. Verbrugge y , Sebastian Gehlert * y , Lian E. M. Stadhouders , Daniel Jacko 3 , Thorben Aussieker 3, Gerard M. J. de Wit 4, Ilse S. P. Vogel 4, Carla Offringa 4, 1 4, , 1, , Martin Schönfelder , Richard T. Jaspers * z and Henning Wackerhage * z 1 Department for Sport and Health Sciences, Technical University of Munich, Georg-Brauchle-Ring 60/62, 80992 München/Munich, Germany; [email protected] (S.A.J.V.); [email protected] (M.S.) 2 Department for the Biosciences of Sports, Institute of Sports Science, University of Hildesheim, Universitätsplatz 1, 31141 Hildesheim, Germany 3 Department for Molecular and Cellular Sports Medicine, German Sport University Cologne, 50933 Cologne, Germany; [email protected] (D.J.); [email protected] (T.A.) 4 Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands; [email protected] (L.E.M.S.); [email protected] (G.M.J.d.W.); [email protected] (I.S.P.V.); c.off[email protected] (C.O.) * Correspondence: [email protected] (S.G.); [email protected] (R.T.J.); [email protected] (H.W.); Tel.: +49-5121-883-11951 (S.G.); +31-20-5988463 (R.T.J.); +49-89-289-24480 (H.W.) Joint first authors. y Joint last authors.
    [Show full text]
  • A20 Promotes Melanoma Progression Via the Activation of Akt Pathway
    Ma et al. Cell Death and Disease (2020) 11:794 https://doi.org/10.1038/s41419-020-03001-y Cell Death & Disease ARTICLE Open Access A20 promotes melanoma progression via the activation of Akt pathway Jinyuan Ma1, Huina Wang1,SenGuo1, Xiuli Yi1, Tao Zhao1,YuLiu1,QiongShi1,TianwenGao1,ChunyingLi1 and Weinan Guo1 Abstract Melanoma is the most life-threatening skin cancer with increasing incidence around the world. Although recent advances in targeted therapy and immunotherapy have brought revolutionary progress of the treatment outcome, the survival of patients with advanced melanoma remains unoptimistic, and metastatic melanoma is still an incurable disease. Therefore, to further understand the mechanism underlying melanoma pathogenesis could be helpful for developing novel therapeutic strategy. A20 is a crucial ubiquitin-editing enzyme implicated immunity regulation, inflammatory responses and cancer pathogenesis. Herein, we report that A20 played an oncogenic role in melanoma. We first found that the expression of A20 was significantly up-regulated in melanoma cell lines. Then, we showed that knockdown of A20 suppressed melanoma cell proliferation in vitro and melanoma growth in vivo through the regulation of cell-cycle progression. Moreover, A20 could potentiate the invasive and migratory capacities of melanoma cell in vitro and melanoma metastasis in vivo by promoting epithelial–mesenchymal transition (EMT). Mechanistically, we found that Akt activation mediated the oncogenic effect of A20 on melanoma development, with the involvement of glycolysis. What’s more, the up-regulation of A20 conferred the acquired resistance to Vemurafenib in BRAF-mutant melanoma. Taken together, we demonstrated that up-regulated A20 promoted melanoma progression via the activation of Akt pathway, and that A20 could be exploited as a potential therapeutic target for 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; melanoma treatment.
    [Show full text]
  • Directed Differentiation of Human Embryonic Stem Cells Into Functional Dendritic Cells Through the Myeloid Pathway
    Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway This information is current as Igor I. Slukvin, Maxim A. Vodyanik, James A. Thomson, of September 24, 2021. Maryna E. Gumenyuk and Kyung-Dal Choi J Immunol 2006; 176:2924-2932; ; doi: 10.4049/jimmunol.176.5.2924 http://www.jimmunol.org/content/176/5/2924 Downloaded from References This article cites 57 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/176/5/2924.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway1 Igor I. Slukvin,2*†‡ Maxim A. Vodyanik,† James A. Thomson,†‡§¶ Maryna E. Gumenyuk,* and Kyung-Dal Choi* We have established a system for directed differentiation of human embryonic stem (hES) cells into myeloid dendritic cells (DCs).
    [Show full text]
  • Activation of PGK1 Under Hypoxic Conditions Promotes Glycolysis and Increases Stem Cell‑Like Properties and the Epithelial‑M
    INTERNATIONAL JOURNAL OF ONCOLOGY 57: 743-755, 2020 Activation of PGK1 under hypoxic conditions promotes glycolysis and increases stem cell‑like properties and the epithelial‑mesenchymal transition in oral squamous cell carcinoma cells via the AKT signalling pathway YADONG ZHANG1,2, HONGSHI CAI1,2, YAN LIAO1,2, YUE ZHU1,2, FANG WANG1,2 and JINSONG HOU1,2 1Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology; 2Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, P.R. China Received January 13, 2020; Accepted April 22, 2020 DOI: 10.3892/ijo.2020.5083 Abstract. Although it has been previously documented that a study demonstrate that hypoxia can increase PGK1 expression, hypoxic environment can promote glycolysis and the malignant resulting in the promotion of glycolysis, enhancing stem progression of oral squamous cell carcinoma (OSCC) cell-like properties and EMT by activating AKT signalling in cells, the specific underlying mechanism remains unclear. OSCC. Phosphoglycerate kinase 1 (PGK1) has been previously reported to serve an important role in tumor metabolism. Introduction The aim of the present study was to investigate the effects of hypoxia and PGK1 on glycolysis, stem cell-like properties Oral squamous cell carcinoma (OSCC) is the most prevalent and epithelial-mesenchymal transition (EMT) in OSCC cells. malignant tumour in the oral and maxillofacial region (1). The Cell Counting Kit-8 assays were performed to examine tumor high incidence of oral cancer is attributed to physical, chemical cell viability under hypoxic conditions. Sphere formation, and biological factors. According to the statistics of American immunohistochemistry, western blotting, Transwell assays and Cancer Association, there were about 48,000 newly diagnosed mouse xenograft studies were performed to assess the biological cases of OSCC in 2016, which accounted for 3% of all new effects of PGK1.
    [Show full text]
  • Structures, Functions, and Mechanisms of Filament Forming Enzymes: a Renaissance of Enzyme Filamentation
    Structures, Functions, and Mechanisms of Filament Forming Enzymes: A Renaissance of Enzyme Filamentation A Review By Chad K. Park & Nancy C. Horton Department of Molecular and Cellular Biology University of Arizona Tucson, AZ 85721 N. C. Horton ([email protected], ORCID: 0000-0003-2710-8284) C. K. Park ([email protected], ORCID: 0000-0003-1089-9091) Keywords: Enzyme, Regulation, DNA binding, Nuclease, Run-On Oligomerization, self-association 1 Abstract Filament formation by non-cytoskeletal enzymes has been known for decades, yet only relatively recently has its wide-spread role in enzyme regulation and biology come to be appreciated. This comprehensive review summarizes what is known for each enzyme confirmed to form filamentous structures in vitro, and for the many that are known only to form large self-assemblies within cells. For some enzymes, studies describing both the in vitro filamentous structures and cellular self-assembly formation are also known and described. Special attention is paid to the detailed structures of each type of enzyme filament, as well as the roles the structures play in enzyme regulation and in biology. Where it is known or hypothesized, the advantages conferred by enzyme filamentation are reviewed. Finally, the similarities, differences, and comparison to the SgrAI system are also highlighted. 2 Contents INTRODUCTION…………………………………………………………..4 STRUCTURALLY CHARACTERIZED ENZYME FILAMENTS…….5 Acetyl CoA Carboxylase (ACC)……………………………………………………………………5 Phosphofructokinase (PFK)……………………………………………………………………….6
    [Show full text]
  • Functions of Extracellular Pyruvate Kinase M2 in Tissue Repair and Regeneration
    Georgia State University ScholarWorks @ Georgia State University Biology Dissertations Department of Biology 5-9-2016 Functions of Extracellular Pyruvate Kinase M2 in Tissue Repair and Regeneration Yinwei Zhang Follow this and additional works at: https://scholarworks.gsu.edu/biology_diss Recommended Citation Zhang, Yinwei, "Functions of Extracellular Pyruvate Kinase M2 in Tissue Repair and Regeneration." Dissertation, Georgia State University, 2016. https://scholarworks.gsu.edu/biology_diss/166 This Dissertation is brought to you for free and open access by the Department of Biology at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Biology Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. FUNCTIONS OF EXTRACELLULAR PYTUVATE KINASE M2 IN TISSUE REPAIR AND REGENERATION by YINWEI ZHANG Under the Direction of Zhi-Ren Liu, PhD ABSTRACT Pyruvate kinase M2 (PKM2) is a glycolytic enzyme expressed in highly proliferating cells. Studies of PKM2 have been focused on its function of promoting cell proliferation in cancer cells. Our laboratory previously discovered that extracellular PKM2 released from cancer cells promoted angiogenesis by activating endothelial cell proliferation and migration. PKM2 activated endothelial cells through integrin αvβ3. Angiogenesis and myofibroblast differentiation are key processes during wound healing. In this dissertation, I demonstrate that extracellular PKM2 released from activated neutrophils
    [Show full text]
  • Metabolic Plasticity Is an Essential Requirement of Acquired Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia
    cancers Article Metabolic Plasticity Is an Essential Requirement of Acquired Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia Miriam G. Contreras Mostazo 1,2,3, Nina Kurrle 3,4,5, Marta Casado 6,7 , Dominik Fuhrmann 8, Islam Alshamleh 4,9, Björn Häupl 3,4,5, Paloma Martín-Sanz 7,10, Bernhard Brüne 5,8,11 , 3,4,5 4,9 3,4,5, 1,2,7,12, , Hubert Serve , Harald Schwalbe , Frank Schnütgen y , Silvia Marin * y 1,2,7,12, , and Marta Cascante * y 1 Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Spain; [email protected] 2 Institute of Biomedicine of University of Barcelona, 08028 Barcelona, Spain 3 Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt am Main, Germany; [email protected] (N.K.); [email protected] (B.H.); [email protected] (H.S.); [email protected] (F.S.) 4 German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; [email protected] (I.A.); [email protected] (H.S.) 5 Frankfurt Cancer Institute (FCI), Goethe University, 60590 Frankfurt am Main, Germany; [email protected] 6 Biomedicine Institute of Valencia, IBV-CSIC, 46010 Valencia, Spain; [email protected] 7 CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain; [email protected] 8 Institute of Biochemistry I, Faculty of
    [Show full text]
  • PFKP Antibody A
    Revision 1 C 0 2 - t PFKP Antibody a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 2 1 Web: [email protected] 4 www.cellsignal.com 5 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB, IP H Mk Endogenous 80 Rabbit Q01813 5214 Product Usage Information Application Dilution Western Blotting 1:1000 Immunoprecipitation 1:50 Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity PFKP Antibody detects endogenous levels of total PFKP protein. Species Reactivity: Human, Monkey Source / Purification Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human PFKP protein. Antibodies are purified by protein A and peptide affinity chromatography. Background Phosphofructokinase (PFK) catalyzes the phosphorylation of fructose-6-phosphate in glycolysis (1). There are three isozymes: muscle-type, liver-type, and platelet-type (2,3). Platelet-type phosphofructokinase (PFKP) is expressed in various cell types (4,5). Research studies have shown that genetic variations in PFKP are associated with individuals born small for gestational age that are prone to obesity and diabetes later in adulthood (6). 1. Mediavilla, D. et al. (2008) J Biochem 144, 235-44. 2. Eto, K. et al. (1994) Biochem Biophys Res Commun 198, 990-8. 3. Hannemann, A. et al.
    [Show full text]
  • GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity
    Article GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity Graphical Abstract Authors Sharon M. Louie, Elizabeth A. Grossman, Lisa A. Crawford, ..., Andrei Goga, Eranthie Weerapana, Daniel K. Nomura Correspondence [email protected] In Brief Using a reactivity-based chemoproteomic platform, Louie et al. have identified GSTP1 as a triple-negative breast cancer target that, when inhibited, impairs breast cancer pathogenicity through inhibiting GAPDH activity and downstream metabolism and signaling pathways. Highlights d We used chemoproteomics to profile metabolic drivers of breast cancer d GSTP1 is a novel triple-negative breast cancer-specific target d GSTP1 inhibition impairs triple-negative breast cancer pathogenicity d GSTP1 inhibition impairs GAPDH activity to affect metabolism and signaling Louie et al., 2016, Cell Chemical Biology 23, 1–12 May 19, 2016 ª 2016 Elsevier Ltd. http://dx.doi.org/10.1016/j.chembiol.2016.03.017 Please cite this article in press as: Louie et al., GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity, Cell Chemical Biology (2016), http://dx.doi.org/10.1016/j.chembiol.2016.03.017 Cell Chemical Biology Article GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity Sharon M. Louie,1 Elizabeth A. Grossman,1 Lisa A. Crawford,2 Lucky Ding,1 Roman Camarda,3 Tucker R. Huffman,1 David K. Miyamoto,1 Andrei Goga,3 Eranthie Weerapana,2 and Daniel K. Nomura1,* 1Departments of Chemistry and Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA 2Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA 3Department of Cell and Tissue Biology and Medicine, University of California, San Francisco, San Francisco, CA 94143, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chembiol.2016.03.017 SUMMARY subtypes that are correlated with heightened malignancy and poor prognosis remain poorly understood.
    [Show full text]
  • Therapeutic Targeting of Aldolase a Interactions Inhibits Lung Cancer Metastasis
    Author Manuscript Published OnlineFirst on July 29, 2019; DOI: 10.1158/0008-5472.CAN-18-4080 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis 2 and Prolongs Survival 3 4 Yu-Chan Chang 1, Jean Chiou1, Yi-Fang Yang2, Chia-Yi Su1, Yuan-Feng Lin3, Chia-Ning Yang4, 5 Pei-Jung Lu5, Ming-Shyan Huang 6, Chih-Jen Yang7* and Michael Hsiao 1,8* 6 7 1. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 8 2. Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical 9 University, Kaohsiung, Taiwan. 10 3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11 Taiwan. 12 4. Department of Life Sciences, National University of Kaohsiung, Kaohsiung, Taiwan. 13 5. Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan 14 6. Department of Internal Medicine, E-DA Cancer Hospital, School of Medicine, I-Shou University, 15 Kaohsiung, Taiwan. 16 7. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical 17 University, Kaohsiung, Taiwan. 18 8. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, 19 Taiwan. 20 21 *To whom correspondence should be addressed: 22 Dr. Michael Hsiao, Genomics Research Center, Academia Sinica, 128 Academia Rd., Sec. 2, 23 Nankang-Dist., Taipei, Taiwan. Tel: +886-2-2787-1243, Fax: +886-2-2789-9931, E-mail: 24 [email protected] 25 Or to 1 Downloaded from cancerres.aacrjournals.org on September 27, 2021. © 2019 American Association for Cancer Research.
    [Show full text]