USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1
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 chemore...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/20/3294 |
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| author | Yueh-Te Lin Joseph Lin Yi-En Liu Yun-Cen Chen Shiang-Ting Liu Kai-Wen Hsu Dar-Ren Chen Han-Tsang Wu |
| author_facet | Yueh-Te Lin Joseph Lin Yi-En Liu Yun-Cen Chen Shiang-Ting Liu Kai-Wen Hsu Dar-Ren Chen Han-Tsang Wu |
| author_sort | Yueh-Te Lin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:29:18Z |
| format | Article |
| id | doaj.art-93b89a606a8247e0a89870738014bd5c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:29:18Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-93b89a606a8247e0a89870738014bd5c2023-11-23T23:28:44ZengMDPI AGCells2073-44092022-10-011120329410.3390/cells11203294USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1Yueh-Te Lin0Joseph Lin1Yi-En Liu2Yun-Cen Chen3Shiang-Ting Liu4Kai-Wen Hsu5Dar-Ren Chen6Han-Tsang Wu7Cancer Genome Research Center, Department of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, Guishan District, Taoyuan 333, TaiwanComprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 500, TaiwanCancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanCancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanDepartment of Nursing, Changhua Christian Hospital, Changhua 500, TaiwanResearch Center for Cancer Biology, Institute of New Drug Development, China Medical University, Taichung 404, TaiwanComprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 500, TaiwanCancer Research Center, Changhua Christian Hospital, Changhua 500, TaiwanTriple-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.https://www.mdpi.com/2073-4409/11/20/3294ubiquitin specific protease 7chemoresistancetriple-negative breast cancerATP-binding cassette B1 |
| spellingShingle | Yueh-Te Lin Joseph Lin Yi-En Liu Yun-Cen Chen Shiang-Ting Liu Kai-Wen Hsu Dar-Ren Chen Han-Tsang Wu USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 Cells ubiquitin specific protease 7 chemoresistance triple-negative breast cancer ATP-binding cassette B1 |
| title | USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 |
| title_full | USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 |
| title_fullStr | USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 |
| title_full_unstemmed | USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 |
| title_short | USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1 |
| title_sort | usp7 induces chemoresistance in triple negative breast cancer via deubiquitination and stabilization of abcb1 |
| topic | ubiquitin specific protease 7 chemoresistance triple-negative breast cancer ATP-binding cassette B1 |
| url | https://www.mdpi.com/2073-4409/11/20/3294 |
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