S-Nitrosylation at the intersection of metabolism and autophagy: Implications for cancer

Abstract

Metabolic plasticity, which determines tumour growth and metastasis, is now understood to be a flexible and context-specific process in cancer metabolism. One of the major pathways contributing to metabolic adaptations in eucaryotic cells is autophagy, a cellular degradation and recycling process that is activated during periods of starvation or stress to maintain metabolite and biosynthetic intermediate levels. Consequently, there is a close association between the metabolic adaptive capacity of tumour cells and autophagy-related pathways in cancer. Additionally, nitric oxide regulates protein function and signalling through S-nitrosylation, a post-translational modification that can also impact metabolism and autophagy. The primary objective of this review is to provide an up-to-date overview of the role of S-nitrosylation at the intersection of metabolism and autophagy in cancer. First, we will outline the involvement of S-nitrosylation in the metabolic adaptations that occur in tumours. Then, we will discuss the multifaceted role of autophagy in cancer, the interplay between metabolism and autophagy during tumour progression, and the contribution of S-nitrosylation to autophagic dysregulation in cancer. Finally, we will present insights into relevant therapeutic aspects and discuss prospects for the future.

Keywords: Autophagy; Cancer metabolism; Nitric oxide; S-nitrosylation; Tumour microenvironment.