The interaction between the enzyme transglutaminase 2 (TG2) and fibronectin (FN) is involved in the cell-matrix interactions that regulate cell signaling, adhesion, and migration and play central roles in pathologic conditions, particularly fibrosis and cancer.
We present evidence suggesting that TG2 has a role in human cancer, summarize what is known about the TG2 mechanism of action in a range of cancer types, and discuss TG2 as a cancer therapy target.
Several variant isoforms and non-coding RNAs are present in cancer and this report explored the expression of these transcripts of the TGM2 gene in cancer cell lines after induction with all-trans retinoic acid.
Transglutaminase 2 (TGM2) is a member of the transglutaminase family, and it is reported to be associated with chemoresistance in various types of cancer.
We conclude, for the first time, that TG2 expression is critical for cancer cell adhesion, migration, invasiveness and cancer cell-stemness during RCC progression and dissemination.
Transglutaminase 2 (TG2) is a ubiquitous multifunctional enzyme whose expression has been found to be altered in numerous studies of apoptosis and cell survival; its activity has been found to be increased in many types of cancer, where it is often over-expressed.
Transglutaminase 2 (TGase2, TG2) activity has been implicated in the pathogenesis of a number of unrelated disorders, including celiac, neurological, and renal diseases, and various forms of cancer.
Recently, members of the transglutaminases (TGM) family, especially TGM2, have been implicated in the progression and drug resistance of cancers, but the function of TGM1 in cancer development has been largely overlooked.
The protein-protein crosslinking activity of the enzyme tissue transglutaminase (TG2; EC 2.3.2.13) is associated with the pathogenesis of various diseases, including celiac disease, lung-, liver- and kidney fibrosis, cancer and neurodegenerative diseases.
Based on the observation that TG2 plays an important role in wound healing and inflammation is known to facilitate cancer growth and progression, we discuss the evidence that TG2 can reprogram inflammatory signaling networks that play fundamental roles in cancer progression.
Efforts to understand the molecular drivers of tTG expression in MES GSCs revealed an unexpected link between tTG and a common marker for stem cells and cancer stem cells, Aldehyde dehydrogenase 1A3 (ALDH1A3).
However, the functional consequences of transamidating and G-protein activities of tissue transglutaminase in promoting cancer metastasis are still controversial.
We recently unveiled a positive regulatory loop involving TGM2 (transglutaminase 2)-NFKB/NF-κB signaling, IL6 and autophagy in cancer using mantle cell lymphoma (MCL) as a model system.
Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype.
These results demonstrate a critical role for the compensatory increase in transglutaminase 2 levels in promoting mTORC1 inhibitor resistance and suggest that rational combination therapy may potentially suppress cancer therapy resistance.
For this reason, there is a major emphasis on identifying proteins that can be targeted to kill cancer stem cells or control their growth, and transglutaminase type II (TGM2/TG2) is such a target in epidermal squamous cell carcinoma.
Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth.