Fig. 6: STAT1 and YAP1 act jointly to upregulate SREBPs and lipid biosynthetic pathways.

Venn diagram (a) and Volcano diagram (b) of genes that are commonly upregulated by STAT1 and YAP1 in HCT116 cells. Essential genes of sterol and lipid biosynthetic pathways are indicated in the Volcano diagram. b 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 STAT1 and 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. c Bar plot of biological processes (BP) from gene ontology (GO) significantly enriched in the common set of genes under the control of both YAP1 and STAT1 identified by gene expression profile analysis. d KEGG pathways under the control of STAT1 and YAP1 in HCT116 cells. e This schematic illustrates the cooperative role of STAT1 and YAP1 in promoting SREBP expression and activating the mevalonate pathway in mutant KRAS CRCs. The STAT1–YAP1 axis functions as a feedforward autoregulatory loop that sustains sterol biosynthesis. STAT1, phosphorylated at S727, directly induces the transcription of SREBF1 and SREBF2 genes. Elevated SREBP levels, in turn, enhance mevalonate pathway activity, leading to the prenylation, plasma membrane anchoring and activation of RHO GTPases. This activation promotes further phosphorylation of STAT1 at S727 and stimulates YAP1 nuclear localization and activation. Although YAP1 acts downstream of STAT1, it also reinforces the loop by cooperating with TEAD4 to transcriptionally upregulate SREBF genes. Created in BioRender. Koromilas, A. (2025) https://BioRender.com/nz5wlhr.