Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226014, India.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biochem Pharmacol. 2023 Jun;212:115550. doi: 10.1016/j.bcp.2023.115550. Epub 2023 Apr 13.
Cancer stem cells (CSCs) are a subset of cancer cells with self-renewal ability and tumor initiating properties. Unlike the other non-stem cancer cells, CSCs resist traditional therapy and remain a major cause of disease relapse. With the recent advances in metabolomics, various studies have demonstrated that CSCs have distinct metabolic properties. Metabolic reprogramming in CSCs contributes to self-renewal and maintenance of stemness. Accumulating evidence suggests that rewiring of energy metabolism is a key player that enables to meet energy demands, maintains stemness, and sustains cancer growth and invasion. CSCs use various mechanisms such as increased glycolysis, redox signaling, and autophagy modulation to overcome nutritional deficiency and sustain cell survival. The alterations in lipid metabolism acquired by the CSCs support biomass production through increased dependence on fatty acid synthesis and β-oxidation, and contribute to oncogenic signaling pathways. This review summarizes our current understanding of lipid metabolism in CSCs and how pharmacological regulation of autophagy and lipid metabolism influences CSC phenotype. Increased dependence on lipid metabolism appears as an attractive strategy to eliminate CSCs using therapeutic agents that specifically target CSCs based on their modulation of lipid metabolism.
癌症干细胞（CSCs）是具有自我更新能力和肿瘤起始特性的癌细胞亚群。与其他非干细胞癌细胞不同，CSCs 抵抗传统治疗，仍然是疾病复发的主要原因。随着代谢组学的最新进展，各种研究表明 CSCs 具有独特的代谢特性。CSCs 中的代谢重编程有助于自我更新和维持干细胞特性。越来越多的证据表明，能量代谢的重排是一个关键因素，能够满足能量需求、维持干细胞特性和维持癌症的生长和侵袭。CSCs 使用各种机制，如增加糖酵解、氧化还原信号和自噬调节，以克服营养缺乏并维持细胞存活。CSCs 获得的脂质代谢改变通过增加对脂肪酸合成和β-氧化的依赖来支持生物量的产生，并有助于致癌信号通路。本综述总结了我们目前对 CSCs 中脂质代谢的理解，以及自噬和脂质代谢的药理学调节如何影响 CSC 表型。增加对脂质代谢的依赖似乎是一种有吸引力的策略，可以使用专门针对 CSCs 的治疗剂来消除 CSCs，这些治疗剂基于其对脂质代谢的调节来特异性靶向 CSCs。
