Nitric oxide and tumor metabolic reprogramming.

Nitric oxide (NO) has been highlighted as an important agent in tumor processes. However, a complete understanding of the mechanisms by which this simple diatomic molecule contributes in tumorigenesis is lacking. Evidence is rapidly accumulating that metabolic reprogramming is a major new aspect of NO biology and this review is aimed to summarize recent research progress on this novel feature that expands the complex and multifaceted role of NO in cancer. Therefore, we discuss how NO may influence glucose and glutamine utilization by tumor cells, and its participation in the regulation of mitochondrial function and dynamics, that is an important mechanism through which cancer cells reprogram their metabolism to meet the biosynthetic needs of rapid proliferation. Finally, we also discuss the NO-related metabolic rewiring involved in the modification of the tumor microenvironment to support cancer invasion and the escape from immune system-mediated recognition. Protein S-nitrosylation appears as a common mechanism by which NO signaling reprograms metabolism. Hence, future research is needed on dysregulated S-nitrosylation/denitrosylation in cancer to comprehend the NO-induced metabolic changes in tumor cells and the role of NO in the metabolic crosstalk within tumor microenvironment.