Moonlighting functions of glucose metabolic enzymes and metabolites in cancer

Glucose metabolic enzymes and their metabolites not only provide energy and building blocks for synthesizing macromolecules but also possess non-canonical or moonlighting functions in response to extracellular and intracellular signalling. These moonlighting functions modulate various cellular activities, including gene expression, cell cycle progression, DNA repair, autophagy, senescence and apoptosis, cell proliferation, remodelling of the tumour microenvironment and immune responses. These functions integrate glucose metabolism with other essential cellular activities, driving cancer progression. Targeting these moonlighting functions could open new therapeutic avenues and lead to cancer-specific treatments. Glucose metabolic enzymes and their metabolites provide cells with energy and building blocks for the synthesis of macromolecules. However, it has become clear that they also have non-canonical functions, which modulate various cellular activities. In this Review, Guo et al. discuss how these moonlighting functions can help drive cancer progression.