Estrogen stimulated migration and invasion of estrogen receptor-negative breast cancer cells involves an ezrin-dependent crosstalk between G protein-coupled receptor 30 and estrogen receptor beta signaling
Estrogen stimulated migration and invasion of estrogen receptor-negative breast cancer cells involves an ezrin-dependent crosstalk between G protein-coupled receptor 30 and estrogen receptor beta signaling
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雌激素刺激雌激素受体阴性乳腺癌细胞的迁移和侵袭涉及 G 蛋白偶联受体 30 和雌激素受体 β 信号传导之间依赖埃兹蛋白的串扰。
DOI：
10.1016/j.steroids.2016.01.021
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发表时间：
2016-07-01
期刊：
影响因子：
2.7
通讯作者：
Wang, Tinghuai
中科院分区：
文献类型：
--
作者：
Zhou, Kewen;Sun, Peng;Wang, Tinghuai
雌激素通过膜相关G蛋白偶联受体30（GPR 30）介导雌激素受体阴性（ER-）乳腺癌细胞的重要细胞活动。然而，在这种侵袭性肿瘤中雌激素对细胞运动和侵袭作用的生物学作用和机制仍然知之甚少。我们发现，在ER阴性癌细胞中用17 β-雌二醇（E2）治疗导致ezrin依赖性细胞骨架重排，并对细胞迁移和侵袭产生刺激作用。从机制上讲，E2诱导的埃兹蛋白激活在不同的细胞环境中由不同的机制介导。在具有高GPR 30/ER β比率的SK-BR-3细胞中，GPR 30的沉默能够消除E2诱导的ERK 1/2、AKT磷酸化和ezrin活化，而在具有低GPR 30/ER β比率的MDA-MB-231细胞中，E2刺激的ezrin活化由ER β/PI 3 K/AKT信号通路介导。重要的是，我们发现GPR 30信号传导的激活显著阻止ER β激活诱导的埃兹蛋白磷酸化、细胞迁移和侵袭，表明MDA-MB-231细胞中GPR 30和ER β信号传导之间的拮抗剂效应。这些发现强调了雌激素诱导的细胞运动和ER阴性乳腺癌细胞的侵袭性中不同雌激素受体之间的重要相互作用。(C)2016 Elsevier Inc. All rights reserved.
Estrogen mediates important cellular activities in estrogen receptor negative (ER-) breast cancer cells via membrane associated G protein-coupled receptor 30 (GPR30). However, the biological role and mechanism of estrogen action on cell motility and invasion in this aggressive kind of tumors remains poorly understood. We showed here that treatment with 17 beta-estradiol (E2) in ER-negative cancer cells resulted in ezrin-dependent cytoskeleton rearrangement and elicited a stimulatory effect on cell migration and invasion. Mechanistically, E2 induced ezrin activation was mediated by distinct mechanisms in different cell contexts. In SK-BR-3 cells with a high GPR30/ER beta ratio, silencing of GPR30 was able to abolish E2 induced ERK1/2, AKT phosphorylation and ezrin activation, whereas in MDA-MB-231 cells with low GPR30/ER beta ratio, E2 stimulated ezrin activation was mediated by the ER beta/PI3K/AKT signaling pathway. Importantly, we showed that activation of GPR30 signaling significantly prevents ER beta activation induced ezrin phosphorylation, cell migration and invasion, indicating an antagonist effect between GPR30 and ER beta signaling in MDA-MB-231 cells. These findings highlight the important interplay between different estrogen receptors in estrogen induced cell motility and invasiveness in ER-negative breast cancer cells. (C) 2016 Elsevier Inc. All rights reserved.