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

Cancers
Diego Carrillo-BeltránFrancisco Aguayo

Abstract

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.

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Citations

Aug 13, 2020·Cancers·Francisco AguayoDaniela Nuñez-Acurio
Feb 10, 2021·Biology·Francisco Perez-DominguezFrancisco Aguayo
Dec 15, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Isabelle Poizot-MartinAlain Makinson
Mar 13, 2021·Reviews in Medical Virology·Alfredo Cruz-Gregorio, Ana Karina Aranda-Rivera
Oct 26, 2021·Reviews in Medical Virology·Alfredo Cruz-GregorioJosé Pedraza-Chaverri

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Methods Mentioned

BETA
transfection
immunoprecipitation
ChIP
nuclear translocation
Transfections
Assay
protein assay
Profiler
PCR

Software Mentioned

ImageJ
GraphPad Prism
PROMO
GraphPad
Gene
GenScript
Rotor

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