Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
CityU Shenzhen Research Institute, Nanshan, Shenzhen, China.
Theranostics. 2020 May 30;10(16):7053-7069. doi: 10.7150/thno.41388. eCollection 2020.
Lipids, the basic components of the cell membrane, execute fundamental roles in almost all the cell activities including cell-cell recognition, signalling transduction and energy supplies. Lipid metabolism is elementary for life sustentation that balances activity between synthesis and degradation. An accumulating amount of data has indicated abnormal lipid metabolism in cancer stem cells (CSCs), and that the alteration of lipid metabolism exerts a great impact on CSCs' properties such as the capability of self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. CSCs' formation and maintenance cannot do without the regulation of fatty acids and cholesterol. In normal cells and embryonic development, fatty acids and cholesterol metabolism are regulated by some important signalling pathways (such as Hedgehog, Notch, Wnt signalling pathways); these signalling pathways also play crucial roles in initiating and/or maintaining CSCs' properties, and such signalling is shown to be commonly modulated by the abnormal lipid metabolism in CSCs; on the other hand, the altered lipid metabolism in turn modifies the cell signalling and generates additional impacts on CSCs. Metabolic rewiring is considered as an ideal hallmark of CSCs, and metabolic alterations would be promising therapeutic targets of CSCs for aggressive tumors. In this review, we summarize the most updated findings of lipid metabolic abnormalities in CSCs and prospect the potential applications of targeting lipid metabolism for anticancer treatment.
脂质是细胞膜的基本组成部分,几乎参与了所有细胞活动,包括细胞间识别、信号转导和能量供应。脂质代谢是生命维持的基础,它平衡着合成和降解之间的活性。越来越多的数据表明,癌症干细胞(CSC)存在异常的脂质代谢,脂质代谢的改变对 CSC 的特性,如自我更新、分化、侵袭、转移、药物敏感性和耐药性等,有很大的影响。CSC 的形成和维持离不开脂肪酸和胆固醇的调节。在正常细胞和胚胎发育中,脂肪酸和胆固醇的代谢受一些重要信号通路(如 Hedgehog、Notch、Wnt 信号通路)的调节;这些信号通路在启动和/或维持 CSC 的特性方面也起着至关重要的作用,并且这些信号通常被 CSC 中的异常脂质代谢所调节;另一方面,改变的脂质代谢反过来又改变了细胞信号,并对 CSC 产生额外的影响。代谢重编程被认为是 CSC 的理想特征,代谢改变将成为侵袭性肿瘤 CSC 有前途的治疗靶点。在这篇综述中,我们总结了 CSC 中脂质代谢异常的最新发现,并展望了靶向脂质代谢治疗癌症的潜在应用。