Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus
| Autor: | Enrique Boccardo, Alexandre T. Vessoni, Matheus H. Dias, Marcelo S. Reis, Marcelo Santos da Silva, Hugo A. Armelin, Julianna D. Zeidler, Eduardo Cararo-Lopes |
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| Přispěvatelé: | Instituto Butantan, Universidade de São Paulo (USP), Universidade do Estado de São Paulo, Washington University in St. Louis, Mayo Clinic College of Medicine, Rutgers Cancer Institute of New Jersey |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Transition (genetics) lcsh:Cytology Immunology Autophagy HPV infection Cell Biology Genotoxic Stress Oxidative phosphorylation Biology Cell cycle medicine.disease Article Malignant transformation Stress signalling Cellular and Molecular Neuroscience Mechanisms of disease Macroautophagy Cancer research medicine lcsh:QH573-671 Human papillomavirus Cancer models ONCOPROTEÍNAS |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Cell Death and Disease, Vol 12, Iss 2, Pp 1-16 (2021) Cell Death & Disease Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Made available in DSpace on 2022-04-29T08:45:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Malignant transformation involves an orchestrated rearrangement of cell cycle regulation mechanisms that must balance autonomic mitogenic impulses and deleterious oncogenic stress. Human papillomavirus (HPV) infection is highly prevalent in populations around the globe, whereas the incidence of cervical cancer is 0.15%. Since HPV infection primes cervical keratinocytes to undergo malignant transformation, we can assume that the balance between transforming mitogenic signals and oncogenic stress is rarely attained. We showed that highly transforming mitogenic signals triggered by HRasG12V activity in E6E7–HPV–keratinocytes generate strong replication and oxidative stresses. These stresses are counteracted by autophagy induction that buffers the rapid increase of ROS that is the main cause of genotoxic stress promoted by the oncoprotein. As a result, autophagy creates a narrow window of opportunity for malignant keratinocytes to emerge. This work shows that autophagy is crucial to allow the transition of E6E7 keratinocytes from an immortalized to a malignant state caused by HRasG12V. Center of Toxins Immune-response and Cell Signaling Instituto Butantan Department of Biochemistry Instituto de Química Universidade de São Paulo Department of Chemical and Biological Sciences Instituto de Biociência Universidade do Estado de São Paulo Department of Medicine Washington University in St. Louis Department of Microbiology Instituto de Biociências Universidade de São Paulo Kogod Aging Center Department of Anesthesiology and Perioperative Medicine Mayo Clinic College of Medicine Rutgers Cancer Institute of New Jersey |
| Databáze: | OpenAIRE |
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