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TGFβ 诱导的 FOXS1 控制上皮-间充质转化，并预测肝癌的预后不良。

TGFβ-induced FOXS1 controls epithelial-mesenchymal transition and predicts a poor prognosis in liver cancer.

机构信息

InsermUniv RennesUMR_S 1242ChemistryOncogenesis, Stress SignalingCentre de Lutte contre le Cancer Eugène MarquisService de Chirurgie Hépatobiliaire et DigestiveCHU RennesRennesFrance.

InsermUniv RennesInraeUMR_S 1241NuMeCan (Nutrition, Metabolisms and Cancer)RennesFrance.

出版信息

Hepatol Commun. 2022 May;6(5):1157-1171. doi: 10.1002/hep4.1866. Epub 2021 Nov 26.

DOI:10.1002/hep4.1866
PMID:34825776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9035581/
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).

摘要

转化生长因子β（TGF-β）在肿瘤进展中起着关键作用，特别是作为上皮-间充质转化（EMT）的有效诱导剂。然而，并非所有驱动 TGFβ 诱导的 EMT 的分子效应物都得到了充分表征。在这里，我们报告叉头框 S1（FOXS1）是一种 SMAD（mothers against decapentaplegic）依赖性 TGFβ 诱导的转录因子，它调节 EMT 初始步骤所需基因的表达（例如，snail 家族转录阻遏物 1），并维持肝癌（HCC）细胞中的间充质表型。在人类 HCC 中，我们报告 FOXS1 是低分化和侵袭性肿瘤亚型的生物标志物。重要的是，FOXS1 的表达水平和活性与预后不良（例如，患者生存率降低）相关，不仅在 HCC 中，而且在结肠癌、胃癌和肾癌中也是如此。结论：FOXS1 构成了 TGF-β 促转移臂活跃的肿瘤的临床相关生物标志物（即，可能受益于使用 TGF-β 通路抑制剂的靶向治疗的患者）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/61194b357dc9/HEP4-6-1157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/8b14e195a567/HEP4-6-1157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/321485586200/HEP4-6-1157-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/4015019a7d96/HEP4-6-1157-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/d8a53cd50d50/HEP4-6-1157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/ae75435e7a57/HEP4-6-1157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/b067d35d192d/HEP4-6-1157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/61194b357dc9/HEP4-6-1157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/8b14e195a567/HEP4-6-1157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/321485586200/HEP4-6-1157-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/4015019a7d96/HEP4-6-1157-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/d8a53cd50d50/HEP4-6-1157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/ae75435e7a57/HEP4-6-1157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/b067d35d192d/HEP4-6-1157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757b/9035581/61194b357dc9/HEP4-6-1157-g002.jpg

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