About this Research Topic
Cholesterol (Chol) is a lipid of key biological importance, essential for membrane biogenesis and functionality, cell proliferation, and cell differentiation, however its “popularity” is biased by the fact that hypercholesterolemia represents a main risk factor for cardiovascular disease, neurodegeneration, inflammatory bowel disease and cancer. Chol can be provided by the diet but it is also synthesized through a series of 21 enzymatic steps, in human liver and in several other extrahepatic tissues. It can be the precursor of steroid hormones, biliary acid and other sterols metabolites through which induce a number of specific effects on human physiology. Among Chol metabolites, an increasing attention is drawn by the family of oxidation products termed oxysterols. Taken up by cells through both vesicular and non-vesicular ways or often generated intracellularly, oxysterols have been recently recognized as elective ligands for important nuclear receptors modulating several signaling pathways and contributing to the regulation of cell viability and metabolism.
The outcome of such a complex network of intracellular reactions promoted by these cholesterol oxidation products appears to be dependent by cell types, the dynamic condition of the cellular and tissue environment and the concentration of the oxysterols. For these reasons, knowledge of molecular mechanisms that regulate the balance of cholesterol and oxysterol metabolism in different tissues is of crucial importance to understand the occurrence of various diseases including cancer.
The purpose of this special issue is to collect recent acquisitions on the role of cholesterol and/or oxysterols as a signaling molecules whose alteration can determine the onset or progression of different pathologies including cancer. Consequently, results obtained recently using different therapeutic strategies (statins, sHDLs, etc ...) aimed to decrease cholesterol and its metabolites availability will be also of great interest and will be discussed.
In particular recent evidences that cholesterol could be involved in the regulation of genes implicated in mitochondrial metabolism has opened up a new research area aimed to lower cholesterol to the purpose of reprogramming tumor metabolism.