Impact of the transcription factor TEAD4 on the proliferation and migration of HPV-positive and HPV-negative human keratinocytes.

• Grant number: 25/12531-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Laura Cristina Sichero Vettorazzo
• Grantee: Stefani Faria Oliver
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). São Paulo , SP, Brazil
• Associated research grant: 24/13024-0 - Cellular transcription factors as prognostic biomarker and therapeutic target in tumors induced by human papillomavirus 16 (HPV-16)., AP.R

Abstract

Persistent infections by high-risk HPV (human papillomavirus) are associated with the development of cervical, vaginal and vulvar cancer in women, penile cancer in men in addition to anal and oropharyngeal tumors in both genders. The expression of viral oncoproteins E6 and E7, associated with cell cycle deregulation, is modulated by transcription factors (TFs) that bind to the viral genome long control region (LCR). Among these factors, TEAD4, an FT related to the Hippo pathway, stands out, involved in proliferation, migration and chemoresistance in various tumors. Preliminary data suggest that TEAD4 may modulate the transcriptional activity of the HPV-16 LCR, influencing the expression of E6 and E7. This project aims to evaluate the impact of TEAD4 overexpression on the migration and proliferation of human keratinocytes, either immortalized or not by HPV-16. Primary keratinocytes (PHKs) and keratinocytes immortalized by the HPV-16 LCR-E6/E7 will be used, in which TEAD4 overexpression will be induced. Subsequently, the expression levels of TEAD4 and E6 and E7 oncoproteins will be evaluated through RT-qPCR and Western blot, as well as cell proliferation and migration (wound healing) assays. We expect to better comprehend how TEAD4 contributes to the proliferative and migratory phenotypes associated to HPV-16 infection. The results may indicate TEAD4 as a potential prognostic biomarker and therapeutic target in HPV-induced tumors.