PKM and neoplasm: Unlike HIF1α, c-Myc mainly regulates oxygen-enriched tumor cells by upregulating aerobic glycolysis and mitochondrial activity since c-Myc directly promotes glycolysis and reduces pyruvate kinase 2(PKM2) activity (52), thereby limiting PKM2-mediated phosphoenolpyruvate-pyruvate conversion (i.e., the last irreversible step of glycolysis).