YAP-mediated GPER signaling impedes proliferation and survival of prostate epithelium in benign prostatic hyperplasia

Zhifu Liu; Senmao Li; Shengbin Chen; Jindong Sheng; Zheng Li; Tianjing Lv; Wei Yu; Yu Fan; Jinlong Wang; Wei Liu; Shuai Hu; Jie Jin

iScience (Mar 2024)

YAP-mediated GPER signaling impedes proliferation and survival of prostate epithelium in benign prostatic hyperplasia

Zhifu Liu,
Senmao Li,
Shengbin Chen,
Jindong Sheng,
Zheng Li,
Tianjing Lv,
Wei Yu,
Yu Fan,
Jinlong Wang,
Wei Liu,
Shuai Hu,
Jie Jin

Affiliations

Zhifu Liu: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Senmao Li: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China; Department of Urology, Peking University Shenzhen Hospital, Shenzhen 518036, China
Shengbin Chen: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Jindong Sheng: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China; Department of Gynaecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Zheng Li: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Tianjing Lv: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Wei Yu: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Yu Fan: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China
Jinlong Wang: Department of Urology, Tibet Autonomous Region People’s Hospital, Lhasa 850000, China
Wei Liu: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen 518036, China; Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China
Shuai Hu: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China; Corresponding author
Jie Jin: Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (Male), Molecular Diagnosis and Treatment Center, National Research Center for Genitourinary Oncology, Beijing 100034, China; Department of Urology, Peking University Shenzhen Hospital, Shenzhen 518036, China; Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Corresponding author

Journal volume & issue: Vol. 27, no. 3
p. 109125

Abstract

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Summary: Benign prostatic hyperplasia (BPH) occurs when there is an imbalance between the proliferation and death of prostate cells, which is regulated tightly by estrogen signaling. However, the role of G protein-coupled estrogen receptor (GPER) in prostate cell survival remains ambiguous. In this study, we observed that prostates with epithelial hyperplasia showed increased yes-associated protein 1 (YAP) expression and decreased levels of estrogen and GPER. Blocking YAP through genetic or drug interventions led to reduced proliferation and increased apoptosis in the prostate epithelial cells. Interestingly, GPER agonists produced similar effects. GPER activation enhanced the phosphorylation and degradation of YAP, which was crucial for suppressing cell proliferation and survival. The Gαs/cAMP/PKA/LATS pathway, downstream of GPER, transmitted signals that facilitated YAP inhibition. This study investigated the interaction between GPER and YAP in the prostate epithelial cells and its contribution to BPH development. It lays the groundwork for future research on developing BPH treatments.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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