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The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression

1
Department of Medicine, Campus Bio-Medico University, Via Alvaro del Portillo 21, IT-00128 Rome, Italy
2
Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, IT-00133 Rome, Italy
3
Department of Biomedical Sciences and Surgical Specialties, University of Ferrara, Via Luigi Borsari 46, IT-44121 Ferrara, Italy
4
Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Luigi Borsari 46, IT-44121 Ferrara, Italy
*
Author to whom correspondence should be addressed.
Med. Sci. 2019, 7(2), 19; https://doi.org/10.3390/medsci7020019
Received: 26 November 2018 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 25 January 2019
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
Tissue transglutaminase (transglutaminase type 2; TG2) is the most ubiquitously expressed member of the transglutaminase family (EC 2.3.2.13) that catalyzes specific post-translational modifications of proteins through a calcium-dependent acyl-transfer reaction (transamidation). In addition, this enzyme displays multiple additional enzymatic activities, such as guanine nucleotide binding and hydrolysis, protein kinase, disulfide isomerase activities, and is involved in cell adhesion. Transglutaminase 2 has been reported as one of key enzymes that is involved in all stages of carcinogenesis; the molecular mechanisms of action and physiopathological effects depend on its expression or activities, cellular localization, and specific cancer model. Since it has been reported as both a potential tumor suppressor and a tumor-promoting factor, the role of this enzyme in cancer is still controversial. Indeed, TG2 overexpression has been frequently associated with cancer stem cells’ survival, inflammation, metastatic spread, and drug resistance. On the other hand, the use of inducers of TG2 transamidating activity seems to inhibit tumor cell plasticity and invasion. This review covers the extensive and rapidly growing field of the role of TG2 in cancer stem cells survival and epithelial–mesenchymal transition, apoptosis and differentiation, and formation of aggressive metastatic phenotypes. View Full-Text
Keywords: tissue transglutaminase; cancer stem cells; inflammation; metastasis tissue transglutaminase; cancer stem cells; inflammation; metastasis
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Tabolacci, C.; De Martino, A.; Mischiati, C.; Feriotto, G.; Beninati, S. The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression. Med. Sci. 2019, 7, 19.

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