Cargando…
Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide
BACKGROUND: Androgen receptor (AR) is expressed in approximately 70% of breast tumors. Recent studies increasingly support AR as a potential therapeutic target of AR-positive breast cancer. We have previously reported that deubiquitinase USP14 stabilizes AR proteins by deubiquitination and USP14 inh...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534920/ https://www.ncbi.nlm.nih.gov/pubmed/31126320 http://dx.doi.org/10.1186/s13046-019-1227-7 |
_version_ | 1783421510485016576 |
---|---|
author | Xia, Xiaohong Huang, Chuyi Liao, Yuning Liu, Yuan He, Jinchan Guo, Zhiqiang Jiang, Lili Wang, Xuejun Liu, Jinbao Huang, Hongbiao |
author_facet | Xia, Xiaohong Huang, Chuyi Liao, Yuning Liu, Yuan He, Jinchan Guo, Zhiqiang Jiang, Lili Wang, Xuejun Liu, Jinbao Huang, Hongbiao |
author_sort | Xia, Xiaohong |
collection | PubMed |
description | BACKGROUND: Androgen receptor (AR) is expressed in approximately 70% of breast tumors. Recent studies increasingly support AR as a potential therapeutic target of AR-positive breast cancer. We have previously reported that deubiquitinase USP14 stabilizes AR proteins by deubiquitination and USP14 inhibition results in inhibition of cell growth and tumor progression in AR-positive prostate cancer and breast cancer. The current study aims to explore the anticancer effect of a treatment combining AR antagonist enzalutamide with USP14 inhibition on breast cancer cells. METHODS: The combining effects of enzalutamide and USP14 inhibition on breast cancer cell proliferation and apoptosis and associated cell signaling were evaluated in vitro and in vivo. RESULTS: USP14 inhibition via administration of IU1 or USP14-specific siRNA/shRNA enhanced cell growth inhibition and apoptosis induction by enzalutamide in breast cancer cell lines in vitro and in vivo. Additionally, the combination of enzalutamide with USP14 inhibition/knockdown induced significant downregulation of AR proteins and suppression of AR-related signaling pathways, including Wnt/β-catenin and PI3K/AKT pathways. Moreover, AKT inhibition via MK2206 increased the antiproliferative and proapoptotic effects of enzalutamide+IU1 combined treatment. CONCLUSION: Collectively, our data suggest that USP14 inhibition in combination with enzalutamide represents a potentially new therapeutic strategy for breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1227-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6534920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65349202019-05-30 Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide Xia, Xiaohong Huang, Chuyi Liao, Yuning Liu, Yuan He, Jinchan Guo, Zhiqiang Jiang, Lili Wang, Xuejun Liu, Jinbao Huang, Hongbiao J Exp Clin Cancer Res Research BACKGROUND: Androgen receptor (AR) is expressed in approximately 70% of breast tumors. Recent studies increasingly support AR as a potential therapeutic target of AR-positive breast cancer. We have previously reported that deubiquitinase USP14 stabilizes AR proteins by deubiquitination and USP14 inhibition results in inhibition of cell growth and tumor progression in AR-positive prostate cancer and breast cancer. The current study aims to explore the anticancer effect of a treatment combining AR antagonist enzalutamide with USP14 inhibition on breast cancer cells. METHODS: The combining effects of enzalutamide and USP14 inhibition on breast cancer cell proliferation and apoptosis and associated cell signaling were evaluated in vitro and in vivo. RESULTS: USP14 inhibition via administration of IU1 or USP14-specific siRNA/shRNA enhanced cell growth inhibition and apoptosis induction by enzalutamide in breast cancer cell lines in vitro and in vivo. Additionally, the combination of enzalutamide with USP14 inhibition/knockdown induced significant downregulation of AR proteins and suppression of AR-related signaling pathways, including Wnt/β-catenin and PI3K/AKT pathways. Moreover, AKT inhibition via MK2206 increased the antiproliferative and proapoptotic effects of enzalutamide+IU1 combined treatment. CONCLUSION: Collectively, our data suggest that USP14 inhibition in combination with enzalutamide represents a potentially new therapeutic strategy for breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1227-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-24 /pmc/articles/PMC6534920/ /pubmed/31126320 http://dx.doi.org/10.1186/s13046-019-1227-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xia, Xiaohong Huang, Chuyi Liao, Yuning Liu, Yuan He, Jinchan Guo, Zhiqiang Jiang, Lili Wang, Xuejun Liu, Jinbao Huang, Hongbiao Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title | Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title_full | Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title_fullStr | Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title_full_unstemmed | Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title_short | Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide |
title_sort | inhibition of usp14 enhances the sensitivity of breast cancer to enzalutamide |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534920/ https://www.ncbi.nlm.nih.gov/pubmed/31126320 http://dx.doi.org/10.1186/s13046-019-1227-7 |
work_keys_str_mv | AT xiaxiaohong inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT huangchuyi inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT liaoyuning inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT liuyuan inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT hejinchan inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT guozhiqiang inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT jianglili inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT wangxuejun inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT liujinbao inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide AT huanghongbiao inhibitionofusp14enhancesthesensitivityofbreastcancertoenzalutamide |