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.

包括致癌在内的关键病理信号通路调节满足细胞代谢需求的代谢酶的典型功能。重要的是，这些信号通路还赋予大量代谢酶具有非经典或非代谢功能，称为“月光”功能。在这篇综述中，我们强调了具有此类活性的异常调节的代谢酶如何在广泛的工具性细胞活动的调控中发挥关键作用，包括基因表达、细胞周期进程、DNA 修复、细胞增殖、存活、细胞凋亡和肿瘤微环境重塑，从而促进包括癌症在内的疾病的病理进展。