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).

尽管与人乳头瘤病毒 (HPV) 感染相关的头颈部鳞状细胞癌 (HNSCC) 的发病率最近一直在上升，但其肿瘤发生的潜在机制仍然在很大程度上未知。在这里，我们研究了高表达整合素α6（ITGα6）（HPV 受体之一）的HNSCC 细胞在HPV 感染期间是否有偏好。此外，我们检查了 HPV + ve HNSCC 细胞中 ITGα6 基因功能的获得或丧失，以及其对 HNSCC 患者的预后价值。发现 HPV 假病毒更具传染性，与对照细胞相比，HNSCC 细胞具有过度表达的 ITGα6 基因。ITGα6 的过表达和抑制分别增加和减少了 HPV + ve HNSCC 细胞的干性表型。此外，ITGα6 可以通过部分介导 HPV + ve HNSCC 细胞中的 AKT 通路来调节干性。最后，在 ITGα6 表达升高的情况下，HPV + ve HNSCC 患者预后较差；然而，ITGα6 的表达水平不影响 HPV 阴性 HNSCC 患者的存活率。总之，ITGα6 可以作为 HPV + ve HNSCC 癌样干细胞 (CSC) 的潜在治疗靶点。