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

The epithelial-mesenchymal transition (EMT) is a key process in tumor invasion and migration. Transforming growth factor-beta s (TGF-beta s) are multifunctional growth factors and powerful modulators of the EMT. Here, we investigated the relationship between TGF-beta 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-beta 1 and 02 mRNA expression levels were higher in TNBC cells than those in non-TNBC cells. Thus, we examined the effect of the TGF-beta 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-beta 1 or TGF-beta 2-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-beta 1 or TGF-beta 2 were completely reversed by LY2109761 treatment in HCC1806 TNBC cells. Taken together, we demonstrated that elevated TGF-beta expression triggers invasion and migration by TNBCs through the EMT process. Inhibiting the TGF-beta signaling pathway is considered a promising therapeutic strategy for treating TNBC. (C) 2015 Elsevier Ltd. All rights reserved.