Role of cholesterol homeostasis and its efflux pathways in cancer progression

•Accumulation of cholesterol in the tumor cell plays a pivotal role to facilitate unhindered growth and development.•Key genes involved in cholesterol efflux are SR-B1, ABCA1, ABCG1, LXRs and are poorly understood in cancer pathogenesis.•Cholesterol efflux genes cross talk with major signaling pathways involved in cell proliferation, survival and immunity.•Generally, SR-B1 and ABCG1 behave as oncogene while ABCA1 and LXRs act as tumor suppressors.•Targeting cholesterol efflux genes and associated pathways can be attractive therapeutic targets. Tumor cells show high avidity for cholesterol in order to support their inherent nature to divide and proliferate. This results in the rewiring of cholesterol homeostatic pathways by influencing not only de novo synthesis but also uptake or efflux pathways of cholesterol. Recent findings have pointed towards the importance of cholesterol efflux in tumor pathogenesis. Cholesterol efflux is the first and foremost step in reverse cholesterol transport and any perturbation in this pathway may lead to the accumulation of intracellular cholesterol, thereby altering the cellular equilibrium. This review addresses the different mechanisms of cholesterol efflux from the cell and highlights their role and regulation in context to tumor development. There are four different routes by which cholesterol can be effluxed from the cell namely, 1) passive diffusion of cholesterol to mature HDL particles, 2) SR-B1 mediated facilitated diffusion, 3) Active efflux to apo A1 via ABCA1 and 4) ABCG1 mediated efflux to mature HDL. These molecular players facilitating cholesterol efflux are engaged in a complex interplay with different signaling pathways. Thus, an understanding of the efflux pathways, their regulation and cross-talk with signaling molecules may provide novel prognostic markers and therapeutic targets to combat the onset of carcinogenesis.