Department of Urology, The First Hospital of Jilin University, Changchun 130021, China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Clin Nutr. 2024 Feb;43(2):332-345. doi: 10.1016/j.clnu.2023.12.005. Epub 2023 Dec 9.
Lipids represent the essential components of membranes, serve as fuels for high-energy processes, and play crucial roles in signaling and cellular function. One of the key hallmarks of cancer is the reprogramming of metabolic pathways, especially abnormal lipid metabolism. Alterations in lipid uptake, lipid desaturation, de novo lipogenesis, lipid droplets, and fatty acid oxidation in cancer cells all contribute to cell survival in a changing microenvironment by regulating feedforward oncogenic signals, key oncogenic functions, oxidative and other stresses, immune responses, or intercellular communication. Peroxisome proliferator-activated receptors (PPARs) are transcription factors activated by fatty acids and act as core lipid sensors involved in the regulation of lipid homeostasis and cell fate. In addition to regulating whole-body energy homeostasis in physiological states, PPARs play a key role in lipid metabolism in cancer, which is receiving increasing research attention, especially the fundamental molecular mechanisms and cancer therapies targeting PPARs. In this review, we discuss how cancer cells alter metabolic patterns and regulate lipid metabolism to promote their own survival and progression through PPARs. Finally, we discuss potential therapeutic strategies for targeting PPARs in cancer based on recent studies from the last five years.
脂质是膜的重要组成部分,可作为高能过程的燃料,并在信号转导和细胞功能中发挥关键作用。癌症的一个关键特征是代谢途径的重编程,特别是异常的脂质代谢。癌细胞中脂质摄取、脂质去饱和、从头合成、脂滴和脂肪酸氧化的改变,通过调节反馈致癌信号、关键致癌功能、氧化和其他应激、免疫反应或细胞间通讯,有助于细胞在不断变化的微环境中存活。过氧化物酶体增殖物激活受体 (PPAR) 是被脂肪酸激活的转录因子,作为核心脂质传感器发挥作用,参与脂质动态平衡和细胞命运的调节。除了在生理状态下调节全身能量稳态外,PPAR 在癌症中的脂质代谢中也发挥着关键作用,这一领域正受到越来越多的研究关注,特别是针对 PPAR 的基本分子机制和癌症治疗。在这篇综述中,我们讨论了癌细胞如何通过 PPAR 改变代谢模式和调节脂质代谢来促进自身的存活和进展。最后,我们根据过去五年的最新研究讨论了针对癌症中 PPAR 的潜在治疗策略。