Abstract
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.
Highlights
Despite the increased understanding of cancer cell biology and significant progression in surgery, cancer remains one of the leading causes of mortality worldwide
High-mobility group box 1 plays a pleiotropic role in inflammation and cancer progression [91] and, the interplay between TG2 and high-mobility group box 1 (HMGB1) could be important for future applications in the field of cancer progression
Transglutaminase 2 has been implicated in a large variety of cellular functions, many of which are crucial in tumor cell proliferation, survival, and metastatic spread
Summary
Despite the increased understanding of cancer cell biology and significant progression in surgery, cancer remains one of the leading causes of mortality worldwide. Tissue transglutaminase (TG2) belongs to a family of enzymes (EC 2.3.2.13) that catalyze the post-translational modifications of proteins through a calcium-dependent acyl-transfer reaction between the γ-carboxamide group of a peptide-bound glutamine residue and the ε-amino group of a peptide-bound lysine (or other primary amine), leading to the formation of ε-(γ-glutamyl)lysine crosslinks [13,14]. This key multifunctional enzyme plays an essential role in CSC biology, and in the promotion and metastasis of tumors. This review will provide a brief overview that considers the role of TG2 expression and activity in cancer initiation, survival, and progression
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