Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation
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Gautam Adhikary1, Daniel Grun1, H. Richard Alexander7, Joseph S. Friedberg4,5, Wen Xu1, Jeffrey W. Keillor6, Sivaveera Kandasamy5 and Richard L. Eckert1,2,3,4
1Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA
2Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA
3Department of Reproductive Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA
4Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
5Department of Surgery and Division of General and Surgical Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA
6Department of Chemistry, University of Ottawa, Ottawa, ON, CA
7Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
Richard L. Eckert, email: email@example.com
Keywords: mesothelioma; transglutaminase; TGM2; cancer stem cell; EMT
Received: April 23, 2018 Accepted: September 08, 2018 Published: October 02, 2018
Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.
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