Fig. 9

Schematic illustration of HIF-1α-induced glucose metabolic reprogramming imparts 5-FU resistance in CRC. The cumulative mitochondrial damage in CRC is the primary driver of glucose metabolic reprogramming, which is a shift from OXPHOS to glycolysis and PPP. The 5-FU resistance phenotype in CRC is derived from energy metabolism reprogramming, which arises from HIF-1α upregulation in non-classical ways, by ROS and the Wnt/β-catenin signaling pathway, independently from external oxygen concentrations