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Exp Cell Res ; 407(2): 112815, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34496296

ABSTRACT

Although the incidence rates of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection have recently been on the rise, the underlying mechanism of its tumorigenesis remains largely unknown. Here, we investigated whether HNSCC cells with high expression of integrin alpha 6 (ITGα6), one of the HPV receptors, have a preference during HPV infection. In addition, we examined the gain or loss of function of the ITGα6 gene in HPV + ve HNSCC cells, as well as its prognostic value in patients with HNSCC. HPV pseudovirus was found to be more infective, with HNSCC cells featuring an overexpressed ITGα6 gene compared to the control cells. Overexpression and suppression of ITGα6 respectively increases and decreases stemness phenotypes of HPV + ve HNSCC cells. Furthermore, ITGα6 can regulate stemness by partially mediating AKT pathway in HPV + ve HNSCC cells. Finally, patients with HPV + ve HNSCC had a poor prognosis in cases of elevated ITGα6 expression; however, the expression levels of ITGα6 did not influence the survival rates of HPV-negative HNSCC patients. In conclusion, ITGα6 can serve as a potential therapeutic target for HPV + ve HNSCC cancer-like stem cells (CSCs).


Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/pathology , Integrin alpha6/metabolism , Neoplastic Stem Cells/pathology , Papillomavirus Infections/complications , Squamous Cell Carcinoma of Head and Neck/pathology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/virology , Humans , Integrin alpha6/genetics , Mice , Mice, Nude , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/virology , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Prognosis , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/virology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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