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The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression

Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understandin...

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Autores principales: Xia, Xiaohong, Huang, Chuyi, Liao, Yuning, Liu, Yuan, He, Jinchan, Shao, Zhenlong, Hu, Tumei, Yu, Cuifu, Jiang, Lili, Liu, Jinbao, Huang, Hongbiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997968/
https://www.ncbi.nlm.nih.gov/pubmed/33771975
http://dx.doi.org/10.1038/s41419-021-03607-w
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author Xia, Xiaohong
Huang, Chuyi
Liao, Yuning
Liu, Yuan
He, Jinchan
Shao, Zhenlong
Hu, Tumei
Yu, Cuifu
Jiang, Lili
Liu, Jinbao
Huang, Hongbiao
author_facet Xia, Xiaohong
Huang, Chuyi
Liao, Yuning
Liu, Yuan
He, Jinchan
Shao, Zhenlong
Hu, Tumei
Yu, Cuifu
Jiang, Lili
Liu, Jinbao
Huang, Hongbiao
author_sort Xia, Xiaohong
collection PubMed
description Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understanding of ERα regulation is critical to shape evolutional treatments for breast cancer. By exploring the regulatory mechanisms of ERα at levels of post-translational modifications, we identified the deubiquitinase USP15 as a novel protector for preventing ERα degradation and a critical driver for breast cancer progression. Specifically, we demonstrated that USP15 promoted the proliferation of ERα(+), but not ERα(-) breast cancer, in vivo and in vitro. Meanwhile, USP15 knockdown notably enhanced the antitumor activities of tamoxifen on breast cancer cells. Importantly, USP15 knockdown induced the downregulation of ERα protein via promoting its K48-linked ubiquitination, which is required for proliferative inhibition of breast cancer cells. These findings not only provide a novel treatment for overcoming resistance to endocrine therapy, but also represent a therapeutic strategy on ERα degradation by targeting USP15-ERα axis.
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spelling pubmed-79979682021-04-16 The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression Xia, Xiaohong Huang, Chuyi Liao, Yuning Liu, Yuan He, Jinchan Shao, Zhenlong Hu, Tumei Yu, Cuifu Jiang, Lili Liu, Jinbao Huang, Hongbiao Cell Death Dis Article Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understanding of ERα regulation is critical to shape evolutional treatments for breast cancer. By exploring the regulatory mechanisms of ERα at levels of post-translational modifications, we identified the deubiquitinase USP15 as a novel protector for preventing ERα degradation and a critical driver for breast cancer progression. Specifically, we demonstrated that USP15 promoted the proliferation of ERα(+), but not ERα(-) breast cancer, in vivo and in vitro. Meanwhile, USP15 knockdown notably enhanced the antitumor activities of tamoxifen on breast cancer cells. Importantly, USP15 knockdown induced the downregulation of ERα protein via promoting its K48-linked ubiquitination, which is required for proliferative inhibition of breast cancer cells. These findings not only provide a novel treatment for overcoming resistance to endocrine therapy, but also represent a therapeutic strategy on ERα degradation by targeting USP15-ERα axis. Nature Publishing Group UK 2021-03-26 /pmc/articles/PMC7997968/ /pubmed/33771975 http://dx.doi.org/10.1038/s41419-021-03607-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xia, Xiaohong
Huang, Chuyi
Liao, Yuning
Liu, Yuan
He, Jinchan
Shao, Zhenlong
Hu, Tumei
Yu, Cuifu
Jiang, Lili
Liu, Jinbao
Huang, Hongbiao
The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title_full The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title_fullStr The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title_full_unstemmed The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title_short The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression
title_sort deubiquitinating enzyme usp15 stabilizes erα and promotes breast cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997968/
https://www.ncbi.nlm.nih.gov/pubmed/33771975
http://dx.doi.org/10.1038/s41419-021-03607-w
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