Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus


Publication type
Article
Language
Portuguese
Access rights
Open Access
Appears in Collections:
Metrics
Abstract
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.
Reference
Lopes EC, Dias MH., Silva MS., Zeidler JD., Vessoni AT., Reis MS., et al. Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus. Cell Death Dis.. 2021 Fev;12(194). doi:10.1038/s41419-021-03476-3.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/3565
Journal title
Issue Date
2021


Files in This Item:

Existing users please Login
10.1038s41419-021-03476-3.pdf
Description:
Size: 3.09 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.