Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer

Figure 1 Structure and cellular functions of lipid droplets. Lipid droplets (LDs) have a hydrophobic core of neutral lipids, mainly cholesteryl esters and triglycerides surrounded by a monolayer of phospholipids. LDs are coated with peripheral and integral proteins such as cell death-inducing DFF45-like effector and perilipins proteins, and lipid metabolism enzymes implicated in lipid synthesis and lipolysis: diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2), acyl-CoA cholesterol acyltransferases 1 and 2 (ACAT1 and ACAT2), adipose triglyceride lipase, hormone-sensitive lipase and monoacylglycerol lipase. LDs play roles in energy supply, via fatty acid oxidation, and signalling, by producing lipid intermediates that include pro- and anti-inflammatory signalling molecules and peroxisome proliferator-activated (PPAR) ligands. Upon activation, PPARs together with the coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha form a nuclear complex with RXR that binds to the DNA to activate the transcription of target genes. TAG: Triglycerides; CIDE: Cell death-inducing DFF45-like effector; PLIN: Perilipins; ATGL: Adipose triglyceride lipase; HSL: Hormone-sensitive lipase; MAGL: Monoacylglycerol lipase; FA: Fatty acid; CE: Cholesteryl esters; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; DGAT: Diacylglycerol acyltransferases; ACAT: Acyl-CoA cholesterol acyltransferases; PPARs: Peroxisome proliferator-activated receptors.

Figure 2 Features of cells with high content of lipid droplets. Cells with high lipid droplets (LD) content show activation of different signalling pathways such as Wnt/β-catenin, Hippo/Yes-associated protein, Notch, Hedgehog and PPARs/PGC-1α. Increased LD content has been linked to aggressive phenotypes in tumour cells, such as stemness, tumorigenicity, migration and invasion, metabolic plasticity and chemoresistance. LD: Lipid droplets; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PPARs: Peroxisome proliferator-activated receptors; YAP: Yes-associated protein.