TGFβ‐induced FOXS1 controls epithelial–mesenchymal transition and predicts a poor prognosis in liver cancer
Kevin Bévant, Matthis Desoteux, Gaëlle Angenard, Raphaël Pineau, Stefano Caruso, Corentin Louis, Panagiotis Papoutsoglou, Laurent Sulpice, David Gilot, Jessica Zucman‐Rossi, Cédric Coulouarn
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).