The role of Transglutaminase Type 2 in Breast Cancer

Transglutaminase Type 2 (TG2), member of the Mammalian Transglutaminase family, is a multi-functional and widely distributed protein localized in the cytosol, in the nucleus, in mitochondria, on the plasma membrane, and in the extracellular environment. Based on the interaction with and the availability of different cofactors, TG2 carries out both catalytic and non-catalytic functions. Indeed, it behaves as a transglutaminase or a Gα signalling protein and retains functions of protein disulphide isomerase, protein kinase and scaffolding factor. Given its pleiotropic nature, it’s not surprising that its deregulation has been associated with a variety of human diseases, including cancer. Interestingly, its role in the tumoral context is highly debated since it was described to act both as an oncogenic and a tumour-suppressor factor in a tumour-specific way. Our work aims at investigating TG2 involvement in the Triple Negative Breast Cancer subtype, which is molecularly characterized by the deficiency of the major therapeutic targets: estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Overall, our data shed light on the role of TG2 in shaping Breast Cancer progression and aggressiveness. Specifically, we evaluate TG2 impact on cancer cell metabolism and mitochondrial functions to delineate metabolic vulnerabilities of therapeutic interest.