癌症中的脂质代谢异质性。
The Heterogeneity of Lipid Metabolism in Cancer.
机构信息
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
出版信息
Adv Exp Med Biol. 2021;1311:39-56. doi: 10.1007/978-3-030-65768-0_3.
The study of cancer cell metabolism has traditionally focused on glycolysis and glutaminolysis. However, lipidomic technologies have matured considerably over the last decade and broadened our understanding of how lipid metabolism is relevant to cancer biology [1-3]. Studies now suggest that the reprogramming of cellular lipid metabolism contributes directly to malignant transformation and progression [4, 5]. For example, de novo lipid synthesis can supply proliferating tumor cells with phospholipid components that comprise the plasma and organelle membranes of new daughter cells [6, 7]. Moreover, the upregulation of mitochondrial β-oxidation can support tumor cell energetics and redox homeostasis [8], while lipid-derived messengers can regulate major signaling pathways or coordinate immunosuppressive mechanisms [9-11]. Lipid metabolism has, therefore, become implicated in a variety of oncogenic processes, including metastatic colonization, drug resistance, and cell differentiation [10, 12-16]. However, whether we can safely and effectively modulate the underlying mechanisms of lipid metabolism for cancer therapy is still an open question.
癌症细胞代谢的研究传统上集中在糖酵解和谷氨酰胺分解上。然而，脂质组学技术在过去十年中已经成熟了很多，拓宽了我们对脂质代谢与癌症生物学的相关性的理解[1-3]。研究表明，细胞脂质代谢的重编程直接有助于恶性转化和进展[4,5]。例如，新的脂质合成可以为增殖的肿瘤细胞提供构成新子细胞的质膜和细胞器膜的磷脂成分[6,7]。此外，线粒体β-氧化的上调可以支持肿瘤细胞的能量代谢和氧化还原稳态[8]，而脂质衍生的信使可以调节主要的信号通路或协调免疫抑制机制[9-11]。因此，脂质代谢与多种致癌过程有关，包括转移性定植、耐药性和细胞分化[10,12-16]。然而，我们是否可以安全有效地调节脂质代谢的潜在机制来进行癌症治疗仍然是一个悬而未决的问题。
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