Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway

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Jun-Jun QiuKeqin Hua

Abstract

Background The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. Methods A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. Results HPV 16/18 E6 upregulated Wnt7b expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nom...Continue Reading

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