Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

Zonca, Sara, Pinton, Giulia, Wang, Zhuo, Soluri, Maria Felicia, Tavian, Daniela, Griffin, Martin, Sblattero, Daniele and Moro, Laura (2017). Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia. Cell Death and Disease, 8 (2),

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.

Publication DOI: https://doi.org/10.1038/cddis.2017.30
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Immunology,Cellular and Molecular Neuroscience,Cell Biology,Cancer Research
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2017-02-02
Authors: Zonca, Sara
Pinton, Giulia
Wang, Zhuo
Soluri, Maria Felicia
Tavian, Daniela
Griffin, Martin
Sblattero, Daniele
Moro, Laura

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