Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
FEBS J. 2018 Feb;285(3):432-443. doi: 10.1111/febs.14281. Epub 2017 Oct 23.
Metabolic activity of malignant cells is very different from that of their nontransformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. In particular, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this for therapeutic benefit. Alterations in lipid metabolism are one of the main aspects of metabolic rewiring of transformed cells. Up-regulation of several lipogenic enzymes has been reported to be a characteristic of various cancer types. Lysophosphatidic acid (LPA), a simple byproduct of the lipid biosynthesis pathway, has gained immense importance due to its elevated level in several cancers and associated growth-promoting activity. Importantly, a current study revealed its role in increased de novo lipid synthesis through up-regulation of sterol regulatory element-binding protein 1, a master regulator of lipid metabolism. This review summarizes the recent insights in the field of oncolipid LPA-mediated signaling in regard to lipid metabolism in cancers. Future work in this domain is required to understand the up-regulation of the de novo synthesis pathway and the role of its end products in malignant cells. This will open a new arena of research toward the development of specific metabolic inhibitors that can add to the pre-existing chemotherapeutics in order to increase the efficacy of clinical output in cancer patients.
恶性细胞的代谢活性与未转化的等效细胞非常不同,这将代谢重编程确立为每个转化细胞的重要标志。特别是,目前该领域的研究旨在了解致癌信号对转化细胞代谢重编程的调节作用,以便将其用于治疗益处。脂质代谢的改变是转化细胞代谢重编程的主要方面之一。据报道,几种生脂酶的上调是各种癌症类型的特征。溶血磷脂酸(LPA)是脂质生物合成途径的简单副产物,由于其在几种癌症中的升高水平及其相关的促生长活性,其重要性得到了极大的提高。重要的是,目前的一项研究揭示了它通过上调固醇调节元件结合蛋白 1(脂质代谢的主要调节剂)来增加从头脂质合成的作用。这篇综述总结了关于癌症中脂质代谢的 Oncolipid LPA 介导信号领域的最新见解。需要在该领域开展进一步的工作,以了解从头合成途径的上调及其终产物在恶性细胞中的作用。这将为开发特定的代谢抑制剂开辟一个新的研究领域,这些抑制剂可以与现有的化疗药物联合使用,以提高癌症患者的临床疗效。