Suppression of CUL4A attenuates TGF-β1-induced epithelial-to-mesenchymal transition in breast cancer cells

Abstract

Transforming growth factor-β1 (TGF-β1) plays a vital role in the process of epithelial-to-mesenchymal transition (EMT) in breast cancer and the cullin 4A (CUL4A) gene is overexpressed in primary breast cancer. However, whether TGF-β1 signaling can induce CUL4A expression has not been investigated to date, at least to the best of our knowledge. In this study, using breast cancer cell lines, we found that the CUL4A expression level was increased following EMT induced by TGF-β1. Silencing CUL4A expression or CUL4A inhibition by thalidomide suppressed the EMT process induced by TGF-β1. We also found that CUL4A was associated with the expression of zinc finger E-box-binding homeobox 1 (ZEB1) which was induced by TGF-β1. These results suggest that CUL4A is upregulated in TGF-β1-induced EMT, and has a regulatory function in this process. The identification of CUL4A as a downstream target of TGF-β1 represents a critical pro-survival mechanism in breast cancer progression and provides another point for therapeutic intervention in breast cancer.