@article{263bdb3b6de84b4488774f44966d03ad,
title = "Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination",
abstract = " It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER - )/AR-positive (AR + ) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G 0 /G 1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer. ",
author = "Yuning Liao and Xiaohong Xia and Ningning Liu and Jianyu Cai and Zhiqiang Guo and Yanling Li and Lili Jiang and Dou, {Q. Ping} and Daolin Tang and Hongbiao Huang and Jinbao Liu",
note = "Funding Information: Acknowledgments We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. The study was supported by the National Natural Science Foundation of China (81472390, 81472762, and 31671435), the National Funds for Developing Local Colleges and Universities (B16056001), the Science and Technology Program of Guangzhou (201604020001), Pearl River S&T Nova Program of Guangzhou (201506010071), Innovative Academic Team of Guangzhou Education System (1201610014), General Project (1201610098) from Guangzhou Education Commission, the Science and Technology Planning Project of Guangdong Province, China (2014A020212691 and 2016A030308), a Research Award Fund for Outstanding Young Teachers in Guangdong Provincial Higher Education Institutions (YQ2015136), the Project of Department of Education of Guangdong Province(2016KTSCX118, 2016KTSCX119), a Research Scholar Grant from the American Cancer Society (RSG-16-014-01-CDD), the National Institutes of Health, USA (R01CA160417 and R01GM115366), the Natural Science Foundation of Guangdong Province (2016A030308011), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2017). We thank the Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University for flow cytometry analysis. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = apr,
day = "1",
doi = "10.1038/s41388-017-0069-z",
language = "English (US)",
volume = "37",
pages = "1896--1910",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "14",
}