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铁死亡中的脂质代谢:揭示癌症中的关键机制和治疗潜力

Lipid metabolism in ferroptosis: Unraveling key mechanisms and therapeutic potential in cancer.

作者信息

Lee Jaewang, Roh Jong-Lyel

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; Department of Biomedical Science, General Graduate School, CHA University, Pocheon, Republic of Korea.

出版信息

Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189258. doi: 10.1016/j.bbcan.2024.189258. Epub 2024 Dec 31.

Abstract

Ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation, has emerged as a critical area of research for cancer therapy. This review delves into the intricate relationship between lipid metabolism and ferroptosis, emphasizing the impact of lipidome remodeling on cancer cell susceptibility. We explore key mechanisms, such as the role of polyunsaturated fatty acids and phosphatidylethanolamines in ferroptosis induction, alongside the protective effects of monounsaturated fatty acids and their regulatory enzymes. We also discuss the influence of dietary fatty acids, lipid droplets, and the epithelial-to-mesenchymal transition on ferroptosis and cancer resistance. By integrating current findings on enzymatic regulation, lipid peroxidation pathways, and metabolic adaptations, this review highlights potential therapeutic strategies targeting lipid metabolism to enhance ferroptosis-based cancer treatments. Our goal is to provide a comprehensive overview that underscores the significance of lipid metabolic pathways in ferroptosis and their implications for developing novel cancer therapies.

摘要

铁死亡是一种由脂质过氧化驱动的铁依赖性细胞死亡形式,已成为癌症治疗研究的一个关键领域。本综述深入探讨了脂质代谢与铁死亡之间的复杂关系,强调了脂质组重塑对癌细胞易感性的影响。我们探讨了关键机制,如多不饱和脂肪酸和磷脂酰乙醇胺在铁死亡诱导中的作用,以及单不饱和脂肪酸及其调节酶的保护作用。我们还讨论了膳食脂肪酸、脂滴以及上皮-间质转化对铁死亡和癌症抗性的影响。通过整合当前关于酶调节、脂质过氧化途径和代谢适应的研究结果,本综述强调了针对脂质代谢以增强基于铁死亡的癌症治疗的潜在治疗策略。我们的目标是提供一个全面的概述,强调脂质代谢途径在铁死亡中的重要性及其对开发新型癌症治疗方法的意义。

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