Transglutaminase 2 in cancer

The significant influence of tumor microenvironment on malignant cells has been investigated with enthusiasm in this era of targeted therapy. Transglutaminase 2 (TG2, EC 2.3.2.13), a multi-functional enzyme that catalyzes the formation of intermolecular isopeptide bonds between glutamine and lysine side-chains, has been reported to exert important pathophysiological functions. The aim of this review was to investigate the correlation between TG2 and malignant behaviors, which could provide the rationale for novel approaches in anti-cancer therapy. We performed a systematic and electronic search on Medline, Scopus, and Web of Science for relevant publications from inception to April 2015. The bibliographic references of retrieved articles were further reviewed for additional relevant studies. TG2 exerts important physiological functions and plays vital roles in inflammation mainly through its modulation on the structure and stability of extracellular matrix (ECM). It also regulates EMT of diverse malignant cells through various intracellular and extracellular pathways. TG2 also plays an important role in tumor progression and may serve as a novel prognostic biomarker and therapeutic target in various cancer types. TG2 promotes malignant cell mobility, invasion, and metastasis, and induces chemo-resistance of cancer cells, mainly through its pro-crosslink and signaling transduction mediation propensities. In conclusion, TG2 plays vital roles in malignancy progression, and may have important prognostic and therapeutic significances.