Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.

Transglutaminase 2 (TG2) has emerged as a key cancer cell survival factor that drives epithelial to mesenchymal transition, angiogenesis, metastasis, inflammation, drug resistance, cancer stem cell survival and stemness, and invasion and migration. TG2 can exist in a GTP-bound signaling-active conformation or in a transamidase-active conformation. The GTP bound conformation of TG2 contributes to cell survival and the transamidase conformation can contribute to cell survival or death. 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.