Activation of GPR30 stimulates GTP-binding of Gαi1 protein to sustain activation of Erk1/2 in inhibition of prostate cancer cell growth and modulates metastatic properties
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摘要Previously, we reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. Mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. Here we report that G-1, through GPR30, activated Gαi1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase (AC) for cAMP production in PCa cells. The chemical-induced activation of AC-cAMP-PKA signaling attenuated Erk1/2 activity and blocked the cell growth inhibitory effects of G-1. Furthermore, PCa predominantly expressed Gαi1 proteins. Silencing of Gαi1 expression blocked the inhibitory effects of G-1 on PCa cell growth. By gene expression profiling, GPR30 activation by G-1 interfered expression of cell cycle regulators and machinery elements to modulate PCa cell growth and the RACGAP1 interactome to control metastatic properties. In this regard, we demonstrated that G-1 inhibited PCa cell migration and invasion with reduced formations of filopodia and stress fibers through a GPR30-dependent pathway. Taken together, our findings revealed the underlying mechanism for sustaining Erk1/2 activation upon GPR30 activation by G-1 in PCa cells and the GPR30-mediated pathways in controlling PCa cell growth and metastatic properties.
著者Lau KM, Ma FM, Xia JT, Chan QK, Ng CF, To KF
期刊名稱Experimental cell research
出版年份2017
月份1
日期1
卷號350
期次1
頁次199 - 209
國際標準期刊號0014-4827
語言英式英語
關鍵詞G protein-coupled estrogen receptor, G-1, GPER, Invasion, Migration

上次更新時間 2021-18-01 於 00:59