Supplementary Table S4: Loss of oncogenic B-Raf signaling induces transcripts associated with intestinal differentiation. Description of genes linked to intestinal differentiation and listed in Figure 5B. Depending on the differential regulation over time, genes might appear in only one cell line heat-map as only the top 50 hits is shown for each cell line. However, if a significant change in expression between DMSO and PLX4720 treated samples was detected, the gene is listed for the other cell line as well (see Supplementary Table S2). The arrows mark the mean direction of regulation over the time course. The abundance of transcripts at the individual experimental time points is shown in Supplementary Fig. S8.

Gene Cell line Description Ref. name GSTA1 Colo-205 , Glutathione-S transferase; increased expression was reported for (1, 2) HT29  differentiation Caco-2 cells AKR1B10 Colo-205  Aldo-keto-reductase; highly expressed in small intestine and colon under (3) HT29  physiological circumstances HPGD Colo-205 , Prostaglandine catabolism acting in antagonistic fashion to COX2; Negatively (4-8) HT29  regulated by -Catenin in colorectal cancer cell lines; Highly expressed in differentiated murine and human intestinal cells; Loss-of-expression in human colon cancer; Tumor suppressor in the APCMin mouse model; Deletion of the murine Hpgd gene confers celecoxib resistance; Potential Cdx-2 target gene KRT13 HT29  Keratin; upregulated during vitamin D induced differentiation of KRAS-mutant (9) SW480 colon cancer cells MAOA Colo-205  Mono-amin-oxidase, upregulated during vitamin D induced differentiation of (9) KRAS-mutant SW480 colon cancer cells RARRES1 Colo-205 , Highly expressed in terminally differentiated colorectal mucosa; (10, 11) HT29  Downregulation of RARRES1 is related to stage D progression; Implicated as tumor suppressor in various entities CLDN1 Colo-205 , Claudin-1; tight junction component; see main text for details HT29  CLDN15 Colo-205  Claudin-15; tight junction component; see main text for details CLDN18 Colo-205  Claudin-18; tight junction component; see main text for details CES1 Colo-205  Carboxylesterase 1; Potential Cdx-2 target gene (2, 12) NRARP Colo-205  Notch1 target gene product with ankyrin repeats and negative feedback (13) regulator of this pathway; Expression of NRARP in murine intestinal tissues, tumors and human CRC cell lines is positively correlated with expression of Cdx-1 and Cdx-2 AMACR Colo-205 , -Methylacyl-CoA racemase involved in β-oxidation of branched fatty and bile (12, 14-16) HT29  acids; In normal colonic mucosa, expression is restricted to the surface epithelium directly contacting the intestinal lumen; Expression is high in well to moderately differentiated but not in anaplastic CRCs; Potential Cdx-2 target gene; Loss of AMACR expression more frequently observed in proximal than distal CRCs; Lack of staining or low-intensity staining correlated with poor differentiation status, mucinous histology, lympho-vascular invasion and microsatellite instability UGT2B17 Colo-205  UDP-glucuronosyltransferase, highly upregulated in differentiating Caco-2 (17) cells MYO1A Colo-205 , Myosin expressed in the apical brush border of enterocytes; Frequently (18, 19) HT29  mutated or silenced in CRC; Acts as tumor suppressor upon ectopic expression in human CRC lines VAV3 Colo-205  RhoGEFs regulating cytoskeletal dynamics; Vav3 is predominantly expressed (20) in apical regions of murine terminally differentiating cecal and colonic enterocytes PVRL3 HT29  Cell adhesion molecule of the nectin family localized to adherens junctions; (19) Increased expression was reported for differentiation in Caco-2 cells NDRG1 Colo-205 , Upregulated during colonic differentiation; ectopic expression in human CRC (21, 22) HT29  lines induces hallmarks of differentiation and suppresses their invasive and metastatic potential TFF3 Colo-205 , Cdx-2 target gene and goblet cell differentiation marker; Component of (23, 24) HT29  intestinal mucus. PROM1 Colo-205 , Discussed as a marker of cancer stem cells in a variety of tumor entities; In (25) HT29  normal colon tissue, however, Prominin1 is primarily expressed on the membrane of well-differentiated, Cdx-2-positive cells of the surface epithelium TXNIP Colo-205 , Thioredoxin-interacting protein; Highly upregulated in differentiated colonic (26) HT29  epithelium HMGCS2 Colo-205 , Expression of 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) increases (27) HT29  during differentiation of Caco-2 cells; Suppressed by Myc; Lost in poorly differentiated CRC; Responsive to histone deacetylase inhibitors References for Supplementary Table S4:

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