THE INTERPLAY BETWEEN TRANSGLUTAMINASE TYPE 2 AND DIET IN BREAST CANCER PROGRESSION

Transglutaminase Type 2 (TG2) is a multifunctional and ubiquitously expressed protein, member of the Transglutaminase proteins family. Its main function is the transamidating activity, which is modulated by several cofactors, including calcium and GTP/GDP levels. Moreover, TG2 is involved in regulating several cellular processes including cell survival, cell metabolism, protein degradation, inflammation and angiogenesis. Therefore, given its pleiotropic nature, its deregulation has been involved in multiple pathological conditions, 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. In particular, in Triple Negative Breast Cancer (TNBC), the most aggressive Breast Cancer subtype, TG2 is overexpressed and it is considered a negative prognostic factor since it sustains the metastatic process and the insurgence of drug resistance. Our data confirm a significant role for TG2 in shaping TNBC metabolism and progression. Moreover, we demonstrate that different nutrients availability and intake could be a strategy to modify TG2 expression, finally affecting tumour cells aggressiveness. Overall, our data show that modulating TG2 expression through a proper dietary regimen in combination with existing treatments may represent a new promising therapeutic strategy, finally impacting on patients’ prognosis.