CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis
Abstract Drug resistance occurs frequently in triple-negative breast cancer (TNBC) and leads to early relapse and short survival. Targeting the DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-28355-z |
| _version_ | 1811171729910792192 |
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| author | Depeng Wang Wei Xu Minghua Huang Wei Ma Yulu Liu Xingchen Zhou Qingrui Yang Kun Mu |
| author_facet | Depeng Wang Wei Xu Minghua Huang Wei Ma Yulu Liu Xingchen Zhou Qingrui Yang Kun Mu |
| author_sort | Depeng Wang |
| collection | DOAJ |
| description | Abstract Drug resistance occurs frequently in triple-negative breast cancer (TNBC) and leads to early relapse and short survival. Targeting the DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle progression, but its role in TNBC chemotherapy resistance remains unclear. Here, we found that CENPF, which is highly expressed in TNBC, is associated with a poor prognosis in patients receiving chemotherapy. In addition, in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 cells and ADR-resistant cells (MDA-MB-231/ADR). Then, we demonstrated that CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb to compete with E2F1 in TNBC. Considering the crucial role of E2F1 in the DNA damage response and DNA repair, a novel mechanism by which CENPF regulates the Rb-E2F1 axis will provide new horizons to overcome chemotherapy resistance in TNBC. |
| first_indexed | 2024-04-10T17:19:59Z |
| format | Article |
| id | doaj.art-eaa22ad8a2c24f9699b993b066a6e85f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T17:19:59Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-eaa22ad8a2c24f9699b993b066a6e85f2023-02-05T12:13:13ZengNature PortfolioScientific Reports2045-23222023-01-0113111010.1038/s41598-023-28355-zCENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axisDepeng Wang0Wei Xu1Minghua Huang2Wei Ma3Yulu Liu4Xingchen Zhou5Qingrui Yang6Kun Mu7Department of Pathology, School of Basic Medical Sciences, Shandong UniversityDepartment of Rheumatology and Immunology, Shandong Provincial Hospital, Shandong UniversityDepartment of Respiratory Medicine, Shandong Provincial Third Hospital, Shandong UniversityDepartment of Pathology, School of Basic Medical Sciences, Shandong UniversityDepartment of Pathology, School of Basic Medical Sciences, Shandong UniversityDepartment of Pathology, The Second Hospital of Shandong UniversityDepartment of Rheumatology and Immunology, Shandong Provincial Hospital, Shandong UniversityDepartment of Pathology, School of Basic Medical Sciences, Shandong UniversityAbstract Drug resistance occurs frequently in triple-negative breast cancer (TNBC) and leads to early relapse and short survival. Targeting the DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle progression, but its role in TNBC chemotherapy resistance remains unclear. Here, we found that CENPF, which is highly expressed in TNBC, is associated with a poor prognosis in patients receiving chemotherapy. In addition, in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 cells and ADR-resistant cells (MDA-MB-231/ADR). Then, we demonstrated that CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb to compete with E2F1 in TNBC. Considering the crucial role of E2F1 in the DNA damage response and DNA repair, a novel mechanism by which CENPF regulates the Rb-E2F1 axis will provide new horizons to overcome chemotherapy resistance in TNBC.https://doi.org/10.1038/s41598-023-28355-z |
| spellingShingle | Depeng Wang Wei Xu Minghua Huang Wei Ma Yulu Liu Xingchen Zhou Qingrui Yang Kun Mu CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis Scientific Reports |
| title | CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis |
| title_full | CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis |
| title_fullStr | CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis |
| title_full_unstemmed | CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis |
| title_short | CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis |
| title_sort | cenpf knockdown inhibits adriamycin chemoresistance in triple negative breast cancer via the rb e2f1 axis |
| url | https://doi.org/10.1038/s41598-023-28355-z |
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