Cholesterol: The driving force behind the remodeling of tumor microenvironment in colorectal cancer

Abstract

Essential membrane components and metabolites with a wide range of biological roles are both produced by cholesterol metabolism. Cell-intrinsic and cell-extrinsic stimuli alter cholesterol metabolism in the tumor microenvironment (TME), which in turn encourages colorectal carcinogenesis. Metabolites produced from cholesterol play intricate roles in promoting the development of colorectal cancer (CRC) and stifling immunological responses. By altering the extracellular matrix of the main tumor, redesigning its immunological environment, and altering its mechanical stiffness, cholesterol can encourage the epithelial-mesenchymal transition of the primary tumor, opening up a pathway for tumor metastasis. Its functions in TME remodeling and tumor prevention have been recently identified. In this review we address the function of cholesterol in TME remodeling and therapeutic techniques designed to block cholesterol metabolism, and discuss how combining these strategies with already available anti-CRC medicines can have combined effects and open up new therapeutic avenues.

Keywords

• CRC
• Cholesterol
• Biomarkers
• Targeted therapy
• Tumor microenvironment remodeling