Transglutaminase 2: A keystone in the molecular puzzle of cancer

Abstract

Transglutaminase-2 (TG2), an enzyme also referred to as tissue transglutaminase, is ubiquitously present in a wide range of tissues, cell types, and subcellular compartments. Extensive research has demonstrated its involvement in both physiological cellular processes and pathological conditions. Studies investigating the diverse range of actions and multitude of targets associated with TG2 have significantly contributed to the understanding of its role in various types of cancer. This association is established through its interaction with pathways implicated in the initiation, progression, and ultimate spread of tumors. Furthermore, recent findings indicate that TG2 has a role in modifying the biomechanical milieu and signaling inside the tumor microenvironment, alongside mediating cancer cell behavior and intracellular signaling. In this review, we aim to elucidate the existing understanding of TG2’s involvement in cancer, with a specific emphasis on its functions in translating external signals into the initiation of oncogenic processes. Enhanced comprehension of these pathways may potentially pave the way for novel treatment approaches aimed at modulating this versatile protein.