Zhou Xin, Wang Shuyang, Wang Zhen, Feng Xu, Liu Peng, Lv Xian-Bo, Li Fulong, Yu Fa-Xing, Sun Yiping, Yuan Haixin, Zhu Hongguang, Xiong Yue, Lei Qun-Ying, Guan Kun-Liang
J Clin Invest. 2015 May;125(5):2123-35. doi: 10.1172/JCI79573. Epub 2015 Apr 20.
The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.
G蛋白偶联雌激素受体（GPER）介导雌激素的基因组效应和非基因组效应，并与乳腺癌的发生发展有关。在此，我们比较了乳腺浸润性导管癌（IDC）患者癌组织和相邻正常组织中GPER的表达情况，确定GPER在癌细胞中高度上调。此外，我们的研究表明，GPER刺激通过Gαq-11、PLCβ/PKC和Rho/ROCK信号通路激活Yes相关蛋白1（YAP）和具有PDZ结合结构域的转录共激活因子（TAZ），这两种同源转录共激活因子是Hippo肿瘤抑制通路的关键效应因子。TAZ是GPER诱导的基因转录、乳腺癌细胞增殖和迁移以及肿瘤生长所必需的。此外，在人IDC标本中，TAZ表达与GPER表达呈正相关。总之，我们的结果表明，Hippo/YAP/TAZ通路是GPER的关键下游信号分支，在乳腺肿瘤发生中起关键作用。
