Human Papillomavirus 16 E7 Promotes EGFR/PI3K/AKT1/NRF2 Signaling Pathway Contributing to PIR/NF-κB Activation in Oral Cancer Cells

Carrillo-Beltrán, Diego; Muñoz, Juan P.; Guerrero-Vásquez, Nahir; Blanco, Rancés; de Souza Lino, Vanesca; Tapia, Julio C; Maldonado, Edio; Dubois-Camacho, Karen; Hermoso, Marcela A; Corvalán, Alejandro H; Calaf, Gloria M.; Boccardo, Enrique; Aguayo, Francisco

Keywords: cancer, oncoprotein, papillomavirus, oral, pirin: NF-kB


A subset of oral carcinomas is etiologically related to high-risk human papillomavirus (HR-HPV) infection, with HPV16 being the most frequent HR-HPV type found in these carcinomas. The oncogenic role of HR-HPV is strongly dependent on the overexpression of E6 and E7 oncoproteins, which, in turn, induce p53 and pRb degradation, respectively. Additionally, it has been suggested that HR-HPV oncoproteins are involved in the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducing cancer progression and metastasis. Previously, we reported that HPV16 E7 oncoprotein promotes Pirin upregulation resulting in increased epithelial–mesenchymal transition (EMT) and cell migration, with Pirin being an oxidative stress sensor and activator of NF-κB. In this study, we demonstrate the mechanism by which HPV16 E7-mediated Pirin overexpression occurs by promoting EGFR/PI3K/AKT1/NRF2 signaling, thus causing PIR/NF-κB activation in oral tumor cells. Our results demonstrate a new mechanism by which E7 contributes to oral cancer progression, proposing PIR as a potential new therapeutic target.

Más información

Título de la Revista: CANCERS
Volumen: ND
Número: ND
Editorial: MDPI
Fecha de publicación: 2020
Página de inicio: 1
Página final: 22
Idioma: English
Financiamiento/Sponsor: Fondecyt