Elevated TGF-β1 and -β2 expression accelerates the epithelial to mesenchymal transition in triple-negative breast...

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.