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 G0/G1 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.
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Authors | Yuning Liao, Xiaohong Xia, Ningning Liu, Jianyu Cai, Zhiqiang Guo, Yanling Li, Lili Jiang, Q Ping Dou, Daolin Tang, Hongbiao Huang, Jinbao Liu |
Journal | Oncogene
(Oncogene)
Vol. 37
Issue 14
Pg. 1896-1910
(04 2018)
ISSN: 1476-5594 [Electronic] England |
PMID | 29353883
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- AR protein, human
- Enzyme Inhibitors
- Receptors, Androgen
- USP14 protein, human
- Ubiquitin Thiolesterase
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Topics |
- Apoptosis
(drug effects, physiology)
- Breast Neoplasms
(metabolism)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Female
- Humans
- MCF-7 Cells
- Receptors, Androgen
(metabolism)
- Signal Transduction
(drug effects)
- Ubiquitin Thiolesterase
(antagonists & inhibitors, physiology)
- Ubiquitination
(drug effects)
- Up-Regulation
(drug effects)
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