Fig. 1

A Aerobic glycolysis in cancer. The transportation of extracellular glucose to the cytoplasm is achieved by glucose transporters (GLUTs). Hexokinase (HK) catalyzes the conversion of glucose to glucose-6-phosphate (G6P) and the conversion of Glucose-6-phosphate to fructose-6-phosphate (F6P) is a reversible reaction. The F6P can be catalyzed into fructose-1,6-biphosphate (F1,6BP) by phosphofructokinase1 (PFK-1). F1,6BP is converted into phosphoenolpyruvate (PEP) through a series of reversible reactions. Pyruvate kinase (PK) was responsible for catalyzing PEP into pyruvate and pyruvate can reversibly transformed to lactate by lactate dehydrogenase (LDH). Finally, lactate is transported out of cells which relies on the monocarboxylate transporter/MCT family. Carbonic anhydrases IX (CAIX) can export redundant protons and lactate and maintain the acid–base balance. In addition, the intermediates in glycolysis can enter other metabolic processes including hexosamine pathway, pentose phosphate pathway, lipid metabolism, TCA cycle, amino acid metabolism and one-carbon metabolism to synthesize biomacromolecules and meet the urgent growth needs of tumors. Arrows indicate positive modulations or transitions, while blunt ends indicate negative modulations. B The genetic phenotype in CRC regulates glycolysis. Mutations in APC lead to β-catenin/TCF transcriptional activation which induces increased transcription of β-catenin target genes to increase glycolysis. Inactivating mutations or deletion in the TP53 gene inhibits HIF1A, MYC, GLUTs, HK2, F2,6BP and MCT1 to reduce glycolysis. p53-induced upregulation of parkin can accelerate the degradation of HIF1. Activating mutations in RAS and the overexpression of EGFR trigger the activation of downstream pathways including PI3K/AKT/mTORC1 axis to promote glycolysis by enhancing glucose uptake, phosphorylating glycolytic enzymes and transcriptionally regulating glucose transporters and glycolytic enzymes expression via transcription factors such as HIF1A and MYC. Arrows indicate positive modulations or transitions, while blunt ends indicate negative modulations