The Evolving Landscape of Noncanonical Functions of Metabolic Enzymes in Cancer and Other Pathologies

Key pathological, including oncogenic, signaling pathways regulate the canonical functions of metabolic enzymes that serve the cellular metabolic needs. Importantly, these signaling pathways also confer a large number of metabolic enzymes to have noncanonical or nonmetabolic functions that are referred to as “moonlighting” functions. In this review, we highlight how aberrantly regulated metabolic enzymes with such activities play critical roles in the governing of a wide spectrum of instrumental cellular activities, including gene expression, cell-cycle progression, DNA repair, cell proliferation, survival, apoptosis, and tumor microenvironment remodeling, thereby promoting the pathologic progression of disease, including cancer. Xu et al. review the current understanding of the moonlighting functions of aberrantly regulated metabolic enzymes, which are critical in the pathologic progression of diseases, including cancer. These moonlighting functions are involved in a wide spectrum of key cellular activities, including gene expression, cell-cycle progression, DNA repair, cell proliferation, apoptosis, and tumor microenvironment remodeling.