Estrogen regulates Hippo signaling via GPER in breast cancer

Xin Zhou; Shuyang Wang; Zhen Wang; Xu Feng; Peng Liu; Xian Bo Lv; Fulong Li; Fa Xing Yu; Yiping Sun; Haixin Yuan; Hongguang Zhu; Yue Xiong; Qun Ying Lei; Kun Liang Guan

doi:10.1172/JCI79573

Estrogen regulates Hippo signaling via GPER in breast cancer

Xin Zhou, Shuyang Wang, Zhen Wang, Xu Feng, Peng Liu, Xian Bo Lv, Fulong Li, Fa Xing Yu, Yiping Sun, Haixin Yuan, Hongguang Zhu, Yue Xiong, Qun Ying Lei, Kun Liang Guan

Cancer Biology

Research output: Contribution to journal › Article › peer-review

171 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2123-2135
Number of pages	13
Journal	Journal of Clinical Investigation
Volume	125
Issue number	5
DOIs	https://doi.org/10.1172/JCI79573
State	Published - May 1 2015

ASJC Scopus subject areas

General Medicine

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title = "Estrogen regulates Hippo signaling via GPER in breast cancer",

abstract = "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.",

author = "Xin Zhou and Shuyang Wang and Zhen Wang and Xu Feng and Peng Liu and Lv, {Xian Bo} and Fulong Li and Yu, {Fa Xing} and Yiping Sun and Haixin Yuan and Hongguang Zhu and Yue Xiong and Lei, {Qun Ying} and Guan, {Kun Liang}",

year = "2015",

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doi = "10.1172/JCI79573",

language = "English (US)",

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AU - Zhou, Xin

AU - Wang, Shuyang

AU - Wang, Zhen

AU - Feng, Xu

AU - Liu, Peng

AU - Lv, Xian Bo

AU - Li, Fulong

AU - Yu, Fa Xing

AU - Sun, Yiping

AU - Yuan, Haixin

AU - Zhu, Hongguang

AU - Xiong, Yue

AU - Lei, Qun Ying

AU - Guan, Kun Liang

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

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Estrogen regulates Hippo signaling via GPER in breast cancer

Abstract

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