Nonmetabolic functions of metabolic enzymes in cancer development

Metabolism is a fundamental biological process composed of a series of reactions catalyzed by metabolic enzymes. Emerging evidence demonstrates that the aberrant signaling in cancer cells induces nonmetabolic functions of metabolic enzymes in many instrumental cellular activities, which involve metabolic enzyme-mediated protein post-translational modifications, such as phosphorylation, acetylation, and succinylation. In the most well-researched literatures, metabolic enzymes phosphorylate proteins rather than their metabolites as substrates. Some metabolic enzymes have altered subcellular localization, which allows their metabolic products to directly participate in nonmetabolic activities. This review discusses how these findings have deepened our understanding on enzymes originally classified as metabolic enzymes, by highlighting the nonmetabolic functions of several metabolic enzymes responsible for the development of cancer, and evaluates the potential for targeting these functions in cancer treatment.