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

Suppression of CUL4A attenuates TGF-β1-induced epithelial-to-mesenchymal transition in breast cancer cells.
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抑制 CUL4A 可减弱 TGF-β1 诱导的乳腺癌细胞上皮间质转化

DOI:
10.3892/ijmm.2017.3118
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发表时间:
2017-10
影响因子:
5.4
通讯作者:
Wei G
Wei G
中科院分区:
医学3区
文献类型:
--
作者:
Wang Y;Liu X;Zheng H;Wang Q;An L;Wei G

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转化生长因子-β1 (TGF-β1)在乳腺癌的上皮-间质转化(epithelial-to-mesenchymal transition, EMT)过程中起重要作用,cullin 4A (CUL4A)基因在原发性乳腺癌中过表达。然而,TGF-β1信号传导是否能诱导CUL4A表达,至少就我们所知,迄今为止还没有研究。在本研究中,我们利用乳腺癌细胞系,发现TGF-β1诱导EMT后CUL4A表达水平升高。沉默CUL4A表达或沙利度胺抑制CUL4A可抑制TGF-β1诱导的EMT过程。我们还发现CUL4A与TGF-β1诱导的锌指E-box-binding homeobox 1 (ZEB1)表达相关。这些结果表明,CUL4A在TGF-β1诱导的EMT中表达上调,并在此过程中具有调节作用。CUL4A作为TGF-β1的下游靶点的发现,代表了乳腺癌进展中一个关键的促生存机制,为乳腺癌的治疗干预提供了另一个点。
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.
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