title: 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.
abstract: 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 17β-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/ERβ 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/ERβ ratio, E2 stimulated ezrin activation was mediated by the ERβ/PI3K/AKT signaling pathway. Importantly, we showed that activation of GPR30 signaling significantly prevents ERβ activation induced ezrin phosphorylation, cell migration and invasion, indicating an antagonist effect between GPR30 and ERβ 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.
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou 510080, People's Republic of China.
authors: Kewen
authors: K
authors: Zhou
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China; Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510080, People's Republic of China.
authors: Peng
authors: P
authors: Sun
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China.
authors: Yaxing
authors: Y
authors: Zhang
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China.
authors: Xinchao
authors: X
authors: You
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China.
authors: Ping
authors: P
authors: Li
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, People's Republic of China. Electronic address: wangth@mail.sysu.edu.cn.
authors: Tinghuai
authors: T
authors: Wang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D047629:Estrogen Receptor beta; D004967:Estrogens; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D000099149:Ezrin; C109584:GPER1 protein, human
keywords: Cell invasion; Cell migration; ER-negative breast cancer; Estrogen; G protein-coupled receptor 30