Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα).
Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα).
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DOI：
10.1371/journal.pone.0072999
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang HS
中科院分区：
文献类型：
--
作者：
Tsai CL;Wu HM;Lin CY;Lin YJ;Chao A;Wang TH;Hsueh S;Lai CH;Wang HS
雌激素和他莫昔芬（一种抗雌激素）通过基因组和非基因组机制激活雌激素受体（ER）发挥作用，并参与子宫内膜癌的发生。已有研究表明雌二醇和他莫昔芬通过GPR 30（non-genomic ER）信号通路诱导人子宫内膜癌细胞增殖。在此，我们证明了在有或无ERα的子宫内膜癌细胞系中，粘着斑激酶（FAK）的磷酸化参与了雌二醇、他莫昔芬和G1（GPR 30激动剂）诱导的细胞通过跨膜ER（GPR 30）的迁移（石川和RL 95 -2）。此外，通过施用靶向GPR 30的特异性RNA干扰或FAK抑制剂，GPR 30介导的细胞迁移被进一步消除。此外，我们已经验证了GPR 30和磷酸化FAK之间的信号传导确实是由EGFR/PI 3 K/ERK通路介导的。在临床上，在低或无ERα的人子宫内膜癌组织中观察到的GPR 30和磷酸化FAK（pFAK）水平之间的显著相关性进一步表明，雌激素诱导的FAK磷酸化和细胞迁移最可能由GPR 30激活触发。这些结果为了解GPR 30在子宫内膜癌中的病理生理功能提供了新的见解。
Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of estrogen receptor (ER) through genomic and non-genomic mechanisms and are implicated in the development of endometrial cancer. Previous reports have demonstrated that estradiol and tamoxifen induce proliferation of human endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway. Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30 agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines with or without ERα (Ishikawa and RL95-2). Additionally, the GPR30-mediated cell migration was further abolished by administration of either specific RNA interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues with low or without ERα further suggested that estrogen-induced phosphorylation of FAK and cell migration were most likely triggered by GPR30 activation. These results provided new insights for understanding the pathophysiological functions of GPR30 in human endometrial cancers.
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影响因子：
4.7
作者：
Creasman, WT
通讯作者：
Creasman, WT
影响因子：
8
作者：
Chao, A.;Lin, C-Y;Lai, C-H
通讯作者：
Lai, C-H
DOI：
10.1016/s0960-0760(01)00190-x
发表时间：
2002-02-01
影响因子：
4.1
作者：
Filardo, EJ
通讯作者：
Filardo, EJ
影响因子：
--
作者：
Madak-Erdogan, Zeynep;Kieser, Karen J.;Katzenellenbogen, Benita S.
通讯作者：
Katzenellenbogen, Benita S.
影响因子：
--
作者：
Lee, H;Jiang, F;Bai, WL
通讯作者：
Bai, WL