Photo: Jiaming Xue, PhD

Significance

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 cytotoxity and consequently increases the fraction of DBA-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.

By Jiaming Xue, Simone Patergnani, Carlotta Giorgi, Joelle Suarez, Keisuke Goto, Angela Bononi, Mika Tanji, Flavia Novelli, Sandra Pastorino, Ronghui Xu, Natascia Caroccia, A. Umran Dogan, Harvey I. Pass, Mauro Tognon, Paolo Pinton,, Giovanni Gaudino, Tak W. Mak, Michele Carbone, and Haining Yang

 

Proceedings of the National Academy of Sciences in the USA
October 20, 2020 | doi: https://doi.org/10.1073/pnas.2007622117