Fig. 5: YAP1/TEAD4 upregulates SREBFs and sterol biosynthetic genes in mutant KRAS cells.
a Volcano diagram showing the number of differentially expressed genes in YAP1-replete (WT; control) compared to YAP1−/− HCT116 cells. Dashed horizontal and vertical lines indicate significance thresholds (|FC | > 0.5, P < 0.05). A positive fold change means that the gene is upregulated by YAP1. Genes are colored in gray (non-significant), blue (P-value significant), and red (both P-values and fold change are significant). All labeled genes exhibit statistically significant upregulation (logFC > 0.5, P < 0.0005), consistent with their role in cholesterol biosynthesis and lipid metabolism. b Top KEGG pathways under the control of YAP1 in HCT116 cells. c Graphs assess the expression of SREBF1 and 2 mRNAs by qPCR in cells treated with scrambled or YAP1 siRNAs. Gene expressions were normalized to ACTIN and TUBULIN mRNAs used as internal controls. Data were obtained from 3 independent experiments performed in triplicates and represent ±SEM *P < 0.05, **P < 0.01, ***P < 0.001 (t-test). d ChIP-seq data from ENCODE indicating the binding of TEAD4 to transcriptional regulatory regions of SREBF genes. e ChIP assays of YAP1 for binding in complex with TEAD4 to SREBF genes in HCT116 cells, both in the presence and absence of STAT1 and/or YAP1. IgG, non-specific control antibody. f Immunoblotting of SREBP1 and 2 in isogenic pair colon cancer cells prior to and after YAP1 downregulation by siRNAs. FL, full length. g Immunoblotting of SREBP1, 2 and TEAD4 in isogenic pairs of colon cancer cells treated with scrambled or TEAD4 siRNAs. h Immunoblotting of SREBP1 and 2 proteins in HCT116 cells treated with TEAD inhibitor 15 μM VT104 for the indicated time points. f, g, h Quantification of proteins normalized to TUBULIN for each blot is indicated.
