Figure 1.

Lipid biosynthesis in cancer cells. FAs are required by cells to build cell membrane as phospholipids and for energy storage as TG, which is stored in LDs and catabolized in the mitochondria through β-oxidation to provide energy. Lipids can be transported from extracellular source or synthesized by cells using glucose, glutamine, and acetate as carbon source. Cell signaling pathways can also increase lipid biosynthesis. Ligand binding to RTK, which activates PI3K phosphorylation of PIP2 to PIP3, activates AKT and mTOR pathway resulting in activation of the transcription factor SREBP. SREBP can upregulate citrate transporter SLC25A1 and lipid synthesis enzymes ACLY, ACSS2, ACC, FASN, and SCD. Hypoxia also plays a part in lipid biosynthesis, where Hif-1α upregulates glucose uptake, several enzymes in lipid biosynthesis, and reduces flux of glucose to acetyl-CoA through the mitochondria by upregulating PDHK1/4, kinase that inhibits PDH. Enzymes colored in yellow were those targeted with inhibitors. Metabolites are in square white boxes, enzymes are in oval boxes, transcription factors are in hexagonal boxes, and metabolic pathways are in bold and italics. Red arrows represent upregulation of expression by transcription factors.