Changes in the metabolism of cancer cells drive their remarkable adaptability to difficult environmental conditions. The inconsistent supply of nutrients in the cancer microenvironment alters cell signalling pathways and promotes metabolic adaptation. Stressed cancer cells often become dependent on lipid synthesis, uptake and recycling of lipid reserves to survive in nutrient-poor conditions. Here we found that lipid droplet (LD) biogenesis and autophagy are both elevated in MDA-MB-231 breast cancer cells during growth in a medium lacking amino acids (herein referred to as starvation). The increase in the cellular LD content is apparent after 12 h of starvation, it reaches its maximum after 24 h and begins to drop at later time points. The temporal dynamics of the increase in neutral lipid amount during the 24 h period of starvation correlate well with changes in autophagic flux, which indicates a connection between autophagy and LD biogenesis. Our experiments showed that diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis contributes to the survival of MDA-MB-231 breast and HeLa cervical cancer cells during starvation. The latter are more sensitive to amino acid starvation and inhibition of LD biogenesis. Finally, our experiments with autophagy inhibitors showed that autophagy is important for LD biogenesis, but not essential for the survival of breast cancer cells during acute starvation in the absence of amino acids. Our work will contribute to the understanding of the complex interplay between LDs and autophagy and help define their roles in the resistance of cancer cells to stress.
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