CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus-Associated Head and Neck Cancers
| Autor: | Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel Johnson |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis Oncology and Carcinogenesis medicine.disease_cause Article Deubiquitinating enzyme Malignant transformation Metastasis 03 medical and health sciences 0302 clinical medicine Rare Diseases medicine Genetics Humans 2.1 Biological and endogenous factors Oncology & Carcinogenesis Neoplasm Metastasis Dental/Oral and Craniofacial Disease Aetiology Molecular Biology Papillomaviridae Cancer biology Kinase Wnt signaling pathway medicine.disease Head and neck squamous-cell carcinoma Deubiquitinating Enzyme CYLD 030104 developmental biology Infectious Diseases Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis biology.protein Cancer research Disease Progression Sexually Transmitted Infections Signal transduction Developmental Biology |
| Zdroj: | Molecular cancer research : MCR, vol 19, iss 1 Mol Cancer Res |
| Popis: | Genetic alterations of CYLD lysine 63 deubiquitinase (CYLD), a tumor-suppressor gene encoding a deubiquitinase (DUB) enzyme, are associated with the formation of tumors in CYLD cutaneous syndrome. Genome sequencing efforts have revealed somatic CYLD alterations in multiple human cancers. Moreover, in cancers commonly associated with human papillomavirus (HPV) infection (e.g., head and neck squamous cell carcinoma), CYLD alterations are preferentially observed in the HPV-positive versus HPV-negative form of the disease. The CYLD enzyme cleaves K63-linked polyubiquitin from substrate proteins, resulting in the disassembly of key protein complexes and the inactivation of growth-promoting signaling pathways, including pathways mediated by NF-κB, Wnt/β-catenin, and c-Jun N-terminal kinases. Loss-of-function CYLD alterations lead to aberrant activation of these signaling pathways, promoting tumorigenesis and malignant transformation. This review summarizes the association and potential role of CYLD somatic mutations in HPV-positive cancers, with particular emphasis on the role of these alterations in tumorigenesis, invasion, and metastasis. Potential therapeutic strategies for patients whose tumors harbor CYLD alterations are also discussed. Implications: Alterations in CYLD gene are associated with HPV-associated cancers, contribute to NF-κB activation, and are implicated in invasion and metastasis. |
| Databáze: | OpenAIRE |
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