CRH suppressed TGF尾1-induced Epithelial-Mesenchymal Transition via induction of E-cadherin in breast cancer cells
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- 作者：Lai Jin ; Ji ; ong Chen ; Li Li ; Chuanhua Li ; Cheng Chen ; Shengnan Li
- 关键词：Anta ; Antalarmin ; Anti-30 ; Antisauvagine-30 ; CRH ; corticotropin-releasing hormone ; CRHR1 ; corticotropin-releasing hormone receptor 1 ; CRHR2 ; corticotropin-releasing hormone receptor 2 ; EMT ; Epithelial&ndash ; Mesenchymal Transition ; TGF尾1 ; transforming growth factor尾1 ; Ucn ; Urocortin
- 刊名：Cellular Signalling
- 出版年：April, 2014
- 年：2014
- 卷：26
- 期：4
- 页码：757-765
- 全文大小：1471 K
文摘
Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factor尾1 (TGF尾1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cadherin) mainly repressed by Snail1 and Twist1, has been considered as hallmark of Epithelial-Mesenchymal Transition (EMT). Two breast cancer cell lines, MCF-7 and MDA-MB-231 were used to investigate the effect of CRH on TGF尾1-induced EMT by transwell chamber. And HEK293 cells were transiently transfected with CRHR1 or CRHR2 to explore the definite effects of CRH receptor. We reported that CRH inhibited migration of human breast cancer cells through downregulation of Snail1 and Twist1, and subsequent upregulation of E-cadherin. CRH inhibited TGF尾1-mediated migration of MCF-7 via both CRHR1 and CRHR2 while this inhibition in MDA-MB-231 was mainly via CRHR2. Ectopic re-expression of CRHR1 or CRHR2 respectively in HEK293 cells increased E-cadherin expression after CRH stimulation. Furthermore, CRH repressed expression of mesenchymal marker, N-cadherin and induced expression of Occludin, inhibiting EMT in MCF-7 & MDA-MB-231. Our results suggest that CRH may function as a tumor suppressor, at least partly by regulating TGF尾1-mediated EMT. These results may contribute to uncovering the effect of CRH in breast tumorigenesis and progression.