Major pathways of cholesterol metabolism in cancer cells include cholesterol biosynthesis, uptake, efflux, and esterification. Cholesterol is synthesized through the mevalonate pathway in the ER in an extremely complex process: It starts with acetyl-CoA, then mevalonate and squalene are synthesized, and finally cholesterol is generated. Cholesterol uptake depends on the LDLR-mediated endocytosis pathway. Cholesterol efflux is mediated by ABCA1 and ABCG1. Cholesterol is a precursor of CEs, which are generated via the action ACAT1. The transcription of cholesterol metabolism-related genes (such as HMGCR, LDLR, ABCA1, and ABCG1) is mediated by mature SREBP-2. SREBP-2 is cleaved to form mature SREBP-2 in the Golgi apparatus.
