Fig. 1

Alterations in lipid metabolism in CSCs. Both lipid catabolism and anabolism alterations contribute to stemness acquisition in CSCs, including lipid uptake, de novo lipogenesis, lipid desaturation, lipolysis, lipophagy, and FAO. Extracellular FFAs are transported into cells via CD36 and then reused via β-oxidation in mitochondria to release acetyl-CoA. Acetyl-CoA is converted to citrate by citrate synthase and then enters the Krebs cycle for complete oxidation. Alternatively, de novo fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two-carbon units. In addition to lipid catabolism, fatty acids are esterified to glycerol and then triglycerides are stored in lipid droplets. Breakdown of lipids droplets via lipolysis or lipophagy enables stored energy mobilization to the mitochondria. Additionally, saturated fatty acids are desaturated into mono-unsaturated fatty acids by SCD1. Alterations in lipid metabolism not only satisfy energy demands for CSCs proliferation, but also provide essential components for biosynthetic pathways and redox homeostasis. ACC, acetyl-CoA carboxylase; ACLY, ATP citrate lyase; FASN, fatty acid synthase; CD36, cluster of differentiation 36; FAs, fatty acids; MUFAs, mono-unsaturated fatty acids; SCD1, stearoyl-CoA desaturase 1; CPT1, carnitine palmitoyltransferase 1; TCA cycle, tricarboxylic acid cycle; FAO, fatty acid oxidation; and LD, lipid droplet