Role of mTORC2 and nitric oxide in bladder cancer invasion.

504Background: In the United States, bladder cancer is the fourth most common cancer, with an estimated 79,000 new diagnoses and 17,000 deaths in 2017, and the eleventh most common cancer worldwide. The key driver of bladder cancer stage progression is tumor cell invasion which has limited response to current chemotherapy options and hence, newer therapies directed against invasion are key to improving the treatment of bladder cancer. Our laboratory has identified mammalian target of rapamycin complex 2 (mTORC2) as a driver of bladder cancer cell invasion. We have also recently shown that arginine, the nitric oxide (NO) precursor, is implicated in bladder cancer progression. We evaluated the interaction between these two pathways to promote invasion. Methods: Expression of inducible and endothelial nitric oxide synthases (iNOS and eNOS) in FFPE tissue sections of progressive disease was assessed by IHC and correlated with histopathology, progression and stage based on moderate to strong expression (2+, 3+...