Fig. 2

A schematic diagram shows the role of Metabolic reprogramming in the CRC metastasis. CRC cells that metastasize to liver, lung, and peritoneum need to adapt to different metabolic microenvironments to survive and grow at a distant site. During primary tumor metastasis, proliferation is the primary objective, hence there is an increase in pyruvate to lactate conversion. When a cell enters circulation, glutamine metabolism is switched on in order to produce glutathione. Increases in pyruvate and acetyl Co-A, lipid accumulation, and fatty acid uptake all contribute to the modulation of reactive oxygen species-induced damage to these circulating cells, hence enabling cell survival. Upon secondary site seeding, metastasizing cancer cells need to adapt to the metabolic microenvironments of the secondary organ, which mainly includes changes in energy and nutrient sources, organ-specific metabolites, the degree of hypoxia, and the metabolic interactions between organ-specific cells and cancer cells. The processes involve the participation of these molecules, including glucose transporter 3 (Glut3), phosphoenolpyruvate carboxykinase 1 (PCK1), pyruvate, acetyl Co-A, thyroid peroxidase (TPO), lysine, ALDOB aldolase B (ALDOB), superoxide dismutase 1 (SOD1), ATP-citrate lyase (ACLY), Citrate, α-ketoglutarate (α-KG), succinyl-CoA, oxaloacetate, glutamate dehydrogenase (GDH), pyruvate kinase isozymes R/L (PKLR), S-Adenosylmethionine (SAM), forkhead box P3 (FOXP3), matrix metalloproteinase 9 (MMP9), glutaminase 1 (GLS1), hypoxia-inducible factor 1-alpha (HIF-1α), branched-chain ketoacid dehydrogenase kinase (BCKDK), Src, creatine kinase B (CKB), monopolar spindle 1 (MPS1), guanidinoacetate N-methyltransferase (GATM)