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© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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).

Details

Title
TGFβ‐induced FOXS1 controls epithelial–mesenchymal transition and predicts a poor prognosis in liver cancer
Author
Bévant, Kevin 1   VIAFID ORCID Logo  ; Desoteux, Matthis 1   VIAFID ORCID Logo  ; Angenard, Gaëlle 2 ; Pineau, Raphaël 3   VIAFID ORCID Logo  ; Caruso, Stefano 4   VIAFID ORCID Logo  ; Corentin Louis 1   VIAFID ORCID Logo  ; Papoutsoglou, Panagiotis 1   VIAFID ORCID Logo  ; Sulpice, Laurent 1   VIAFID ORCID Logo  ; Gilot, David 3   VIAFID ORCID Logo  ; Jessica Zucman‐Rossi 5   VIAFID ORCID Logo  ; Coulouarn, Cédric 1   VIAFID ORCID Logo 

 Inserm, Univ Rennes, UMR_S 1242, Chemistry, Oncogenesis, Stress Signaling, Centre de Lutte contre le Cancer Eugène Marquis, Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France; Inserm, Univ Rennes, Inrae, UMR_S 1241, NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France 
 Inserm, Univ Rennes, Inrae, UMR_S 1241, NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France 
 Inserm, Univ Rennes, UMR_S 1242, Chemistry, Oncogenesis, Stress Signaling, Centre de Lutte contre le Cancer Eugène Marquis, Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France 
 Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, Paris, France 
 Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, Paris, France; European Hospital Georges Pompidou, AP‐HP, Paris, France 
Pages
1157-1171
Section
Original Articles
Publication year
2022
Publication date
May 2022
Publisher
Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
e-ISSN
2471254X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2653933170
Copyright
© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.