Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy
Abstract
Millions of people have been exposed to asbestos and are at increased risk of developing mesothelioma, an aggressive malignancy resistant to current therapies. Here, we elucidate critical steps in asbestos carcinogenesis: asbestos induces the release of high mobility group box 1 that triggers autophagy. Autophagy activation constitutes a key biological process that allows some mesothelial cells to survive asbestos cytotoxicity and consequently increases the fraction of DNA-damaged human mesothelial cells susceptible to malignant transformation. We found that the inhibition of autophagy using either chloroquine or the antidepressant drug desmethylclomipramine increased asbestos-induced cell death and reduced asbestos-mediated cell transformation. Our data suggest that these Food and Drug Administration-approved drugs might be repurposed to protect high-risk asbestos-exposed individuals from developing mesothelioma.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 30, 2020
- Source ID
- 10.1073/pnas.2007622117
Entities
People
- A. Umran Dogan
- Angela Bononi
- Carlotta Giorgi
- Flavia Novelli
- Giovanni Gaudino
- Haining Yang
- Harvey I Pass
- Jiaming Xue
- Joelle D Sacks
- Keisuke Goto
- Mauro Tognon
- Michele Carbone
- Mika Tanji
- Natascia Caroccia
- Paolo Pinton
- Ronghui Xu
- Sandra Pastorino
- Simone Patergnani
- Tak W. Mak
Organizations
- European Research Council
- Fondazione Umberto Veronesi
- Hiroshima University
- Ministry of Health of Italy
- National Cancer Institute
- National Institute of Environmental Health Sciences
- New York University
- Telethon Foundation
- United States Department of Defense
- University Health Network
- University of Ferrara
- University of Hawaiʻi System
- University of Iowa