Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
Int J Mol Sci. 2019 Jul 24;20(15):3624. doi: 10.3390/ijms20153624.
The deregulation of cancer cell metabolic networks is now recognized as one of the hallmarks of cancer. Abnormal lipid synthesis and extracellular lipid uptake are advantageous modifications fueling the needs of uncontrolled cancer cell proliferation. Fatty acids are placed at the crossroads of anabolic and catabolic pathways, as they are implicated in the synthesis of phospholipids and triacylglycerols, or they can undergo β-oxidation. Key players to these decisions are the long-chain acyl-CoA synthetases, which are enzymes that catalyze the activation of long-chain fatty acids of 12-22 carbons. Importantly, the long-chain acyl-CoA synthetases are deregulated in many types of tumors, providing a rationale for anti-tumor therapeutic opportunities. The purpose of this review is to summarize the last up-to-date findings regarding their role in cancer, and to discuss the related emerging tumor targeting opportunities.
癌细胞代谢网络的失调现在被认为是癌症的标志之一。异常的脂质合成和细胞外脂质摄取是有利的改变,为失控的癌细胞增殖提供了燃料。脂肪酸处于合成代谢和分解代谢途径的交汇点,因为它们参与磷脂和三酰甘油的合成,或者可以进行β-氧化。这些决定的关键因素是长链酰基辅酶 A 合成酶,它是催化 12-22 个碳原子的长链脂肪酸激活的酶。重要的是,长链酰基辅酶 A 合成酶在许多类型的肿瘤中失调,为抗肿瘤治疗机会提供了依据。本综述的目的是总结关于它们在癌症中的作用的最新发现,并讨论相关的新兴肿瘤靶向机会。