Transforming growth factor-?1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis.

ABSTRACT: Molecular mechanism underlying the invasion of oral cancer cells remains to be clarified. We previously demonstrated that transforming growth factor-?1 (TGF-?1) induces the expression of mesenchymal markers in human oral squamous cell carcinoma HSC-4 cells. Intriguingly, the expression of the epithelial-mesenchymal transition-related transcription factor Slug was also significantly upregulated upon TGF-?1 stimulation. However, the mechanism by which Slug transduces the TGF-?1-induced signal to enhance the invasiveness of HSC-4 cells is poorly understood. Proteomic analysis revealed that the expression of matrix metalloproteinase (MMP)-10 was upregulated in TGF-?1-stimulated cells. Additionally, a Boyden chamber assay revealed that the TGF-?1-induced increase in invasiveness of HSC-4 cells was significantly inhibited by MMP-10 small interfering RNA (siRNA). Intriguingly, Slug siRNA suppressed TGF-?1-induced expression of MMP-10. These results suggest that TGF-?1 induces invasion in HSC-4 cells through the upregulation of MMP-10 expression in a Slug-dependent manner. On the other hand, Slug siRNA suppressed TGF-?1-induced Wnt-5b expression. Wnt-5b significantly induced MMP-10 expression, whereas Wnt-5b siRNA suppressed the TGF-?1-induced increase in invasiveness, suggesting that TGF-?1-induced expression of MMP-10 and the resulting upregulation of invasiveness are mediated by Wnt-5b. Overall, these results suggest that TGF-?1 stimulates HSC-4 cell invasion through the Slug/Wnt-5b/MMP-10 signalling axis.

SUBMITTER: Hino M 

PROVIDER: S-EPMC4892396 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature