USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma
Abstract Aberrant epigenetic remodeling events occurred in head and neck squamous cell carcinoma (HNSCC) contribute to tumor stemness and chemotherapy resistance, yet little is known. In this study, we identified that ubiquitin-specific peptidase 10 (USP10) is up-regulated in HNSCC tissues, and high...
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07462-x |
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| author | Yanni Shi Jiawei Ding Xiao Ling Danfeng Xu Yan Shen Xingjun Qin |
| author_facet | Yanni Shi Jiawei Ding Xiao Ling Danfeng Xu Yan Shen Xingjun Qin |
| author_sort | Yanni Shi |
| collection | DOAJ |
| description | Abstract Aberrant epigenetic remodeling events occurred in head and neck squamous cell carcinoma (HNSCC) contribute to tumor stemness and chemotherapy resistance, yet little is known. In this study, we identified that ubiquitin-specific peptidase 10 (USP10) is up-regulated in HNSCC tissues, and high USP10 is associated with poor prognosis of patients. Functionally, USP10 serving as an oncogene potentiates the proliferation and metastasis of HNSCC cells in vitro and in vivo. Mechanistically, USP10 physically interacts with, deubiquitinate, and stabilizes BAZ1A proteins. In addition, BAZ1A complexes with SOX2 to drive the enhancer-promoter interaction and facilitate the recruitment of BRD4, thereby activating the expressions of cancer stem cells (CSCs)-related signature. Therefore, we found that USP10 relied on BAZ1A to enhance HNSCC stemness, progression, and chemotherapy resistance. The pharmacology research implicated that BAZ1A-IN-1, one specific BAZ1A inhibitor, could effectively inhibit HNSCC stemness, distal metastasis, and cisplatin resistance. Together, our study revealed a novel USP10/BAZ1A/stemness axis and one significant therapeutic target for USP10-driven HNSCC. |
| format | Article |
| id | doaj-art-785008702f9446bf9e7e3a8f56e2c4e2 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
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| series | Cell Death and Disease |
| spelling | doaj-art-785008702f9446bf9e7e3a8f56e2c4e22025-08-20T03:10:08ZengNature Publishing GroupCell Death and Disease2041-48892025-04-0116111510.1038/s41419-025-07462-xUSP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinomaYanni Shi0Jiawei Ding1Xiao Ling2Danfeng Xu3Yan Shen4Xingjun Qin5Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologyDepartment of Urology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of MedicineDepartment of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologyDepartment of Urology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of MedicineResearch Center for Experimental Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologyAbstract Aberrant epigenetic remodeling events occurred in head and neck squamous cell carcinoma (HNSCC) contribute to tumor stemness and chemotherapy resistance, yet little is known. In this study, we identified that ubiquitin-specific peptidase 10 (USP10) is up-regulated in HNSCC tissues, and high USP10 is associated with poor prognosis of patients. Functionally, USP10 serving as an oncogene potentiates the proliferation and metastasis of HNSCC cells in vitro and in vivo. Mechanistically, USP10 physically interacts with, deubiquitinate, and stabilizes BAZ1A proteins. In addition, BAZ1A complexes with SOX2 to drive the enhancer-promoter interaction and facilitate the recruitment of BRD4, thereby activating the expressions of cancer stem cells (CSCs)-related signature. Therefore, we found that USP10 relied on BAZ1A to enhance HNSCC stemness, progression, and chemotherapy resistance. The pharmacology research implicated that BAZ1A-IN-1, one specific BAZ1A inhibitor, could effectively inhibit HNSCC stemness, distal metastasis, and cisplatin resistance. Together, our study revealed a novel USP10/BAZ1A/stemness axis and one significant therapeutic target for USP10-driven HNSCC.https://doi.org/10.1038/s41419-025-07462-x |
| spellingShingle | Yanni Shi Jiawei Ding Xiao Ling Danfeng Xu Yan Shen Xingjun Qin USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma Cell Death and Disease |
| title | USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| title_full | USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| title_fullStr | USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| title_full_unstemmed | USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| title_short | USP10 stabilizes BAZ1A to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| title_sort | usp10 stabilizes baz1a to drive tumor stemness via an epigenetic mechanism in head and neck squamous cell carcinoma |
| url | https://doi.org/10.1038/s41419-025-07462-x |
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