Moon Young-Ah
Department of Molecular Medicine, Inha University College of Medicine, Incheon, South Korea.
Anim Cells Syst (Seoul). 2023 Mar 20;27(1):61-71. doi: 10.1080/19768354.2023.2189933. eCollection 2023.
The 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 E, 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 E-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.
结直肠癌的发生发展通常涉及基因改变、健康问题、生活方式和饮食等多种因素的累积影响。膳食脂肪酸似乎会影响结直肠癌的发生和进展。尽管研究结果存在矛盾，但目前关于超长链多不饱和脂肪酸对结直肠癌影响的共识是，二十碳五烯酸和二十二碳六烯酸水平较低，而花生四烯酸水平较高与结直肠癌风险增加有关。膜磷脂中花生四烯酸水平的改变会改变前列腺素E的水平，前列腺素E在多个阶段影响癌细胞的生物学活性。花生四烯酸和其他超长链多不饱和脂肪酸也可以通过不依赖前列腺素E的方式影响肿瘤发生，包括β-连环蛋白的稳定、铁死亡、活性氧生成、转录因子的调节以及从头脂肪生成。最近的研究揭示了合成超长链多不饱和脂肪酸的酶的活性与肿瘤发生和癌症进展之间的关联，尽管其机制尚不清楚。在本研究中，我们综述了多不饱和脂肪酸对肿瘤发生的影响、内源性超长链多不饱和脂肪酸合成途径、花生四烯酸的代谢产物及其对结直肠癌发生和进展的影响，以及支持多不饱和脂肪酸合成途径中相关酶与结直肠癌发生和进展之间关联的现有知识。
