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2017 ; 40
(4
): 1114-1124
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Suppression of CUL4A attenuates TGF-?1-induced epithelial-to-mesenchymal
transition in breast cancer cells
#MMPMID28902348
Wang Y
; Liu X
; Zheng H
; Wang Q
; An L
; Wei G
Int J Mol Med
2017[Oct]; 40
(4
): 1114-1124
PMID28902348
show ga
Transforming growth factor-?1 (TGF-?1) 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-?1 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-?1. Silencing CUL4A expression or CUL4A inhibition by thalidomide
suppressed the EMT process induced by TGF-?1. We also found that CUL4A was
associated with the expression of zinc finger E-box-binding homeobox 1 (ZEB1)
which was induced by TGF-?1. These results suggest that CUL4A is upregulated in
TGF-?1-induced EMT, and has a regulatory function in this process. The
identification of CUL4A as a downstream target of TGF-?1 represents a critical
pro-survival mechanism in breast cancer progression and provides another point
for therapeutic intervention in breast cancer.
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