The role of tissue transglutaminase in kidney cancer

Tissue transglutaminase (TG2) is a ubiquitously expressed enzyme and has versatile functions in extracellular matrix (ECM)-stabilization, cell adhesion and cell survival. Different from the enzymatic activity, TG2 may behave as a cell adhesion signaling molecule via binding to syndecan-4 heparan sulfate proteoglycan and favor integrin ß1-dependent signaling resulting in the maintenance of cell adhesion and cell survival. Early studies suggested that TG2 activity and expression decrease in the primary tumors resulting in ECM destabilization. However, increased TG2 expression in parallel with ß1 integrin contributing to the drug resistance, was reported in the metastatic tumors.Renal cell carcinoma (RCC) is the most common type of kidney cancers. This study investigates the importance of TG2 in RCC by analyzing gene expression and enzymatic activity of TG2 in the tissue samples from the RCC patients along with the RCC cell lines. The results indicated that 34% of RCC tumor tissues showed increased TG2 expression compared to the healthy tissues. Moreover, in 71% of these increased TG2 expression was found to be in parallel with the increased syndecan-4 and integrin ß1 levels. TG2 activity assay results showed that TG2 activity was decreased in most of the tumors. Given that TG2 acts as a matrix-stabilizer, the decreased TG2 activity may subject the stroma of RCC tumor more susceptible to proteolytic degradation allowing increased tumor growth and angiogenesis. Analysis of RCC cell lines also confirmed the results obtained from the RCC patients. This research is the first study to investigate the significance of TG2 in RCC.