Integrin alpha 6 as a stemness driver is a novel promising target for HPV (+) head and neck squamous cell carcinoma

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 (ITG alpha 6), one of the HPV receptors, have a preference during HPV infection. In addition, we examined the gain or loss of function of the ITG alpha 6 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 ITG alpha 6 gene compared to the control cells. Overexpression and suppression of ITG alpha 6 respectively increases and decreases stemness phenotypes of HPV + ve HNSCC cells. Furthermore, ITG alpha 6 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 ITG alpha 6 expression; however, the expression levels of ITG alpha 6 did not influence the survival rates of HPV-negative HNSCC patients. In conclusion, ITG alpha 6 can serve as a potential therapeutic target for HPV + ve HNSCC cancer-like stem cells (CSCs).