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辐射暴露通过稳定 ZEB1 引发三阴性乳腺癌的进展。

Radiation exposure triggers the progression of triple negative breast cancer via stabilizing ZEB1.

机构信息

Department of Oncological Radiotherapy, Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, China.

Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, China.

出版信息

Biomed Pharmacother. 2018 Nov;107:1624-1630. doi: 10.1016/j.biopha.2018.08.026. Epub 2018 Sep 7.

DOI:10.1016/j.biopha.2018.08.026
PMID:30257380
Abstract

Our present study confirmed radiation can promote the in vitro migration and invasion of triple negative breast cancer (TNBC) cells and increase the expression of epithelial-mesenchymal transition (EMT) related transcription factor ZEB1, while had no effect on Snail, Slug or Twist. Knockdown of ZEB1 attenuated radiation induced cell migration and invasion, suggesting that ZEB1 is essential for radiation induced progression of TNBC. Radiation increased the protein stability of ZEB1, while had no effect on its mRNA expression. Particularly, the upregulation of ATM, which can phosphorylate and stabilize ZEB1, was involved in radiation induced upregulation of ZEB1. Collectively, we found that radiation can promote the migration, invasion and EMT of TNBC cells through stabilization of ZEB1 via ATM signals.

摘要

我们目前的研究证实,辐射可以促进三阴性乳腺癌(TNBC)细胞的体外迁移和侵袭,并增加上皮-间充质转化(EMT)相关转录因子 ZEB1 的表达,而对 Snail、Slug 或 Twist 没有影响。ZEB1 的敲低减弱了辐射诱导的细胞迁移和侵袭,表明 ZEB1 对于 TNBC 的辐射诱导进展是必需的。辐射增加了 ZEB1 的蛋白稳定性,而对其 mRNA 表达没有影响。特别是,ATM 的上调参与了辐射诱导的 ZEB1 上调,ATM 可以磷酸化并稳定 ZEB1。总的来说,我们发现辐射可以通过 ATM 信号稳定 ZEB1 来促进 TNBC 细胞的迁移、侵袭和 EMT。

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