Fig. 4.

Metabolic homeostasis in sorafenib resistance. (a) OXPHOS is sustained in liver CSCs, and glutamine, fatty acids and acetate could be alternative energy sources to fuel HCC cells under sorafenib-induced hypoxia and relative glucose deprivation. (b) Redox production including GSH, NAPDH and thioredoxin involves multiple metabolic pathways and plays central role in against sorafenib-induced oxidative stress, especially in EMT process. NRF2 plays the key role in (c) Enhanced proteins, lipids and nucleotides biosynthesis are crucial to maintain cell structure, support DNA repair and supply pro-survival growth signals. Abbreviations: OXPHOS, Oxidative phosphorylation; TCA, tricarboxylic acid cycle; GSH, glutathione; NADPH, nicotinamide adenine dinucleotide phosphate; R5P, Ribose 5-phosphate; ROS, reactive oxygen species.