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

Carrillo-Beltran, Diego; Munoz, Juan P.; Guerrero-Vasquez, Nahir; Blanco, Rances; Leon, Oscar; de Souza Lino, Vanesca; Tapia, Julio C.; Maldonado, Edio; Dubois-Camacho, Karen; Hermoso, Marcela A.; Corvalan, Alejandro H.; Calaf, Gloria M.; Boccardo, Enrique; Aguayo, Francisco


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-kappa B), 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-kappa B. 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-kappa B 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.

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Título según WOS: ID WOS:000558053200001 Not found in local WOS DB
Título de la Revista: CANCERS
Volumen: 12
Número: 7
Editorial: MDPI
Fecha de publicación: 2020


Notas: ISI