Emerging roles of polyunsaturated fatty acid synthesis pathway in colorectal cancer

ABSTRACTThe development of colorectal cancer typically involves the accumulated influences of genetic alterations, medical issues, lifestyle, and diet. Dietary fatty acids appear to affect the tumorigenesis and progression of colorectal cancer. Despite conflicting results, the current consensus on the effects of very long-chain polyunsaturated fatty acids on colorectal cancer is that low levels of eicosapentaenoic acid and docosahexaenoic acid, and high levels of arachidonic acid are associated with an increased risk of colorectal cancer. Altered levels of arachidonic acid in membrane phospholipids can change the levels of prostaglandin E2, which affect the biological activities of cancer cells in multiple stages. Arachidonic acid and other very long-chain polyunsaturated fatty acids can affect tumorigenesis in prostaglandin E2-independent manners as well, including stabilization of β-catenine, ferroptosis, ROS generation, regulation of transcription factors, and de novo lipogenesis. Recent studies have revealed an association between the activities of enzymes synthesizing very long-chain polyunsaturated fatty acids and tumorigenesis and cancer progression, although the mechanisms are still unknown. In this study, PUFA effects on tumorigenesis, the endogenous very long-chain polyunsaturated fatty acid synthesis pathway, metabolites of arachidonic acid and their effects on tumorigenesis and progression of CRC, and current knowledge that supports the association of the enzymes involved in the polyunsaturated fatty acid synthesis pathway with colorectal cancer tumorigenesis and progression are reviewed.