Journal
CELLS
Volume 11, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/cells11203294
Keywords
ubiquitin specific protease 7; chemoresistance; triple-negative breast cancer; ATP-binding cassette B1
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Funding
- Ministry of Science and Technology Summit grant [MOST 110-2314-B-371-007-MY3, MOST 110-2314-B-182A-011]
- Changhua Christian Hospital [111-CCH-IRP-037]
- China Medical University [CMU110-MF-10]
- Drug Development Center, China Medical University from The Featured Areas Research Center Program within Ministry of Education, Taiwan
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This study identified USP7 as a potential therapeutic target for overcoming chemoresistance in triple-negative breast cancer. The research demonstrated that USP7 promotes chemoresistance in TNBC by stabilizing the ABCB1 protein, providing insights into targeted therapy for TNBC patients with acquired resistance.
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer. TNBC does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Cytotoxic chemotherapy and surgery are the current therapeutic strategies for TNBC patients, but the chemoresistance of TNBC limits the efficiency of this strategy and shortens the lifespan of patients. The exploration of targeted therapy is ongoing in TNBC research. The aim of the present study was to identify the mechanism underlying acquired resistance in TNBC through the exploration of the relationship between the expression of USP7 and of ABCB1. We found that ubiquitin specific protease 7 (USP7) is a potential therapeutic target for overcoming the chemoresistance of TNBC. USP7 overexpression increased the chemoresistance of TNBC, while the knockdown of USP7 effectively increased the chemosensitivity of chemoresistant TNBC. A USP7 inhibitor effectively induced apoptosis and suppressed metastasis in chemoresistant TNBC. We further clarified that USP7 is a specific deubiquitinating enzyme for ABCB1 that plays an essential role in drug resistance. USP7 directly interacted with ABCB1 and regulated its stability. We concluded that USP7 promotes the chemoresistance of TNBC by stabilizing the ABCB1 protein.
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