Study of transcriptional effects of FOXS1 silencing and TGF-beta treatment in SNU-449 hepatocellular carcinoma cell line

ABSTRACT: Background & aims: Transforming Growth Factor beta (TGFβ) is a pleiotropic cytokine which controls fundamental cellular processes associated with tumor onset and progression. In hepatocellular carcinoma (HCC), we previously highlighted TGFβ signatures recapitulating its functional duality (i.e. cytostatic versus pro-metastatic features) to discriminate patients with good and poor prognosis. Here, we aimed at characterizing Forkhead Box S1 (FOXS1), a predicted transcription factor that we hypothesize to mediate pro-metastatic properties of TGFβ. Methods: FOXS1 expression was profiled in well-characterized HCC cell lines. Transient loss of function of FOXS1 (siRNA) was combined with functional assays and analysis of epithelial-mesenchymal transition (EMT) markers by western blot and immunofluorescence. Clinical relevance of FOXS1 was determined by integrative genomics. Results: Our data show that FOXS1 is a novel canonical SMAD-dependent TGFβ target. Its expression correlates with a mesenchymal phenotype. FOXS1 mediates pro-metastatic properties of TGFβ by inducing EMT and cell migration. In human HCC, FOXS1 correlates with VIM expression and is highly expressed in specific molecular subtypes associated with a poorer differentiation and no CTNNB1 mutation. FOXS1 expression predicts a poor prognosis (e.g. reduced patient survival) in liver, colon, stomach and kidney cancer. Conclusions: FOXS1 is a novel TGFβ target and a key mediator of EMT. Its induction in cancer is associated with a poor prognosis. Thus, determining the expression of FOXS1 in advanced tumors in which the pro-metastatic arm of TGFβ is activated could help to identify patients who may benefit from targeted therapies using TGFβ inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148795 | GEO | 2022/06/15

REPOSITORIES: GEO