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    Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation

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    Author
    Adhikary, G.
    Grun, D.
    Alexander, H.R.
    Date
    2018
    Journal
    Oncotarget
    Publisher
    Impact Journals LLC
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.18632/oncotarget.26130
    Abstract
    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. Copyright 2018 Impact Journals LLC. All rights reserved.
    Sponsors
    This work was supported by the NIH (CA211909 and CA184027).
    Keyword
    Cancer stem cell
    EMT
    Mesothelioma
    TGM2
    Transglutaminase
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85054230799&doi=10.18632%2foncotarget.26130&partnerID=40&md5=9107b3b17f7ac7a7ba556a53ef81108e; http://hdl.handle.net/10713/9290
    ae974a485f413a2113503eed53cd6c53
    10.18632/oncotarget.26130
    Scopus Count
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