TGFβ‐induced FOXS1 controls epithelial–mesenchymal transition and predicts a poor prognosis in liver cancer

Abstract

Transforming growth factor beta (TGF‐β) plays a key role in tumor progression, notably as a potent inducer of epithelial–mesenchymal transition (EMT). However, all of the molecular effectors driving TGFβ‐induced EMT are not fully characterized. Here, we report that forkhead box S1 (FOXS1) is a SMAD (mothers against decapentaplegic)–dependent TGFβ‐induced transcription factor, which regulates the expression of genes required for the initial steps of EMT (e.g., snail family transcription repressor 1) and to maintain a mesenchymal phenotype in hepatocellular carcinoma (HCC) cells. In human HCC, we report that FOXS1 is a biomarker of poorly differentiated and aggressive tumor subtypes. Importantly, FOXS1 expression level and activity are associated with a poor prognosis (e.g., reduced patient survival), not only in HCC but also in colon, stomach, and kidney cancers. Conclusion: FOXS1 constitutes a clinically relevant biomarker for tumors in which the pro‐metastatic arm of TGF‐β is active (i.e., patients who may benefit from targeted therapies using inhibitors of the TGF‐β pathway).