Physical Interaction between HPV16E7 and the Actin-Binding Protein Gelsolin Regulates Epithelial-Mesenchymal Transition via HIPPO-YAP Axis

Human papillomavirus 16 (HPV16) exhibits a strong oncogenic potential mainly in cervical, anogenital and oropharyngeal cancers. The E6 and E7 viral oncoproteins, acting via specific interactions with host cellular targets, are required for cell transformation and maintenance of the transformed phenotype as well. We previously demonstrated that HPV16E7 interacts with the actin-binding protein gelsolin, involved in cytoskeletal F-actin dynamics. Herein, we provide evidence that the E7/gelsolin interaction promotes the cytoskeleton rearrangement leading to epithelial-mesenchymal transition-linked morphological and transcriptional changes. E7-mediated cytoskeletal actin remodeling induces the HIPPO pathway by promoting the cytoplasmic retention of inactive P-YAP. These results suggest that YAP could play a role in the “de-differentiation” process underlying the acquisition of a more aggressive phenotype in HPV16-transformed cells. A deeper comprehension of the multifaceted mechanisms elicited by the HPV infection is vital for providing novel strategies to block the biological and clinical features of virus-related cancers.