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.