| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2794069 | Cytokine | 2015 | 8 Pages |
•TGF-β1 and β2 expression levels are higher in TNBC cells than in non-TNBC cells.•EMT-related gene signatures are highly expressed in TNBC cells.•Vim, FN, and slug mRNA expression levels dose-dependently decreases in response to LY2109761.•TNBC cell motility also decreases in response to LY2109761.•The reduction in E-cad and induction of vim and FN expression by TGF-β1 or TGF-β2 are completely reversed by LY2109761.
The epithelial–mesenchymal transition (EMT) is a key process in tumor invasion and migration. Transforming growth factor-βs (TGF-βs) are multifunctional growth factors and powerful modulators of the EMT. Here, we investigated the relationship between TGF-β expression and invasion by treated triple-negative breast cancer (TNBC) cells. Our results show that invasion capacity of TNBC cells was markedly higher than that of non-TNBC cells. In addition, EMT-related gene signatures, including vimentin (vim), fibronectin (FN), snail, and slug were highly expressed in TNBC cells. Interestingly, our results show that TGF-β1 and β2 mRNA expression levels were higher in TNBC cells than those in non-TNBC cells. Thus, we examined the effect of the TGF-β receptor I/II inhibitor LY2109761 on EMT-related gene expression and cell motility. Our data show that vim, FN, and slug mRNA expression levels dose-dependently decreased in response to LY2109761. TNBC cell motility also decreased in response to LY2109761. Finally, we investigated the effect of LY2109761 on TGF-β1 or TGF-β2-induced E-cadherin (E-cad), vim, and FN mRNA and protein expression. The reduction in E-cad and induction of vim and FN expression by TGF-β1 or TGF-β2 were completely reversed by LY2109761 treatment in HCC1806 TNBC cells. Taken together, we demonstrated that elevated TGF-β expression triggers invasion and migration by TNBCs through the EMT process. Inhibiting the TGF-β signaling pathway is considered a promising therapeutic strategy for treating TNBC.
