The roles of sirtuins family in cell metabolism during tumor development

Abstract

Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD⁺ dependent protein modifying enzymes, sirtuins (SIRT1-SIRT7) have multiple catalytic functions such as deacetylase, desuccinylase, demalonylase, demyristoylase, depalmitoylase, and/or mono-ADP-ribosyltransferase. They play important roles in regulating cell metabolism, especially in glucose and lipid metabolism, thereby exerting complex functions in either increasing or decreasing malignant characteristics in tumors. This review highlights the major function and its mechanisms of sirtuins in cellular metabolic reprogramming, such as glucose metabolism including aerobic glycolysis (the Warburg effect), oxidative phosphorylation (OXPHOS)/tricarboxylic acid (TCA) cycle and glutamine metabolism; lipometabolism including fatty acid metabolism, cholesterol metabolism, ketone body metabolism and acetate metabolism; as well as leucine metabolism and the urea cycle in tumorigenesis and cancer development.

Keywords: Cell metabolism; Glycolysis; Lipometabolism; Sirtuins; Warburg effect.