研究动态
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癌症干细胞中的脂质代谢动力学:癌症的潜在靶标。

Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.

发表日期:2024
作者: Juan Du, Hai Qin
来源: Frontiers in Pharmacology

摘要:

癌症干细胞(CSC)代表肿瘤内异质细胞的一小部分,具有自我更新和启动肿瘤发生的能力。它们是肿瘤发生、转移、复发和耐药性的潜在驱动因素。最近的研究表明,CSC 的干性保存在很大程度上依赖于其独特的脂质代谢改变,使它们能够通过各种机制维持自身的环境稳态。主要目标包括增加细胞内脂肪酸 (FA) 含量以增强能量供应,促进 FA 的 β-氧化以优化能量利用,以及提升甲羟戊酸 (MVA) 途径以实现胆固醇的有效合成。此外,在 CSC 存在糖酵解阻断的情况下,脂滴 (LD) 可以作为替代能源,从而保护 FA 免遭过氧化。此外,自噬和脂质代谢之间的相互作用促进CSC快速适应化疗引起的恶劣微环境。在这篇综述中,我们全面回顾了最近有关CSCs脂质代谢的研究,并简要概述了LDs、FA、胆固醇代谢和自噬在维持CSCs干性方面所发挥的不可或缺的作用。版权所有©2024 Du和Qin。
Cancer stem cells (CSCs) represent a small subset of heterogeneous cells within tumors that possess the ability to self-renew and initiate tumorigenesis. They serve as potential drivers for tumor initiation, metastasis, recurrence, and drug resistance. Recent research has demonstrated that the stemness preservation of CSCs is heavily reliant on their unique lipid metabolism alterations, enabling them to maintain their own environmental homeostasis through various mechanisms. The primary objectives involve augmenting intracellular fatty acid (FA) content to bolster energy supply, promoting β-oxidation of FA to optimize energy utilization, and elevating the mevalonate (MVA) pathway for efficient cholesterol synthesis. Additionally, lipid droplets (LDs) can serve as alternative energy sources in the presence of glycolysis blockade in CSCs, thereby safeguarding FA from peroxidation. Furthermore, the interplay between autophagy and lipid metabolism facilitates rapid adaptation of CSCs to the harsh microenvironment induced by chemotherapy. In this review, we comprehensively review recent studies pertaining to lipid metabolism in CSCs and provide a concise overview of the indispensable role played by LDs, FA, cholesterol metabolism, and autophagy in maintaining the stemness of CSCs.Copyright © 2024 Du and Qin.