Figure 3: Lipids as central players in cancer biology.
Main mechanisms by which lipids contribute to cancer biology. FA synthesis and uptake support membrane biogenesis to drive cell proliferation and exosome formation. However, since increased SFA levels induce lipotoxicity, desaturation to MUFA is required. As membrane-incorporated PUFA is prone to lipid peroxidation and underlies ferroptotic cell death, multiple mechanisms can be deployed to reduce relative PUFA abundance in the membrane. By increasing lipogenesis, relative SFA and MUFA levels are increased, decreasing relative PUFA levels. Furthermore, PUFAs can be stored in lipid droplets or catabolized through FAO. Besides generating ATP to drive cell survival, metastasis and chemoresistance, FAO can increase the antioxidant potential through GSH synthesis, further offering protection against lipid peroxidaton and ferroptotic cell death. Finally, lipids play crucial roles in cellular and intracellular signaling through regulation of membrane fluidity and lipid rafts, and the synthesis of lipid-derived mediators regulating important aspects in tumor biology such as immune evasion and cellular invasion.