Dang Ngoc-Ha T, Singla Arvind K, Mackay Emily M, Jirik Frank R, Weljie Aalim M
Department of Pharmacology, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg 421, Room 10-113, Philadelphia, Pennsylvania, USA 19104.
Curr Pharm Des. 2014;20(15):2637-47. doi: 10.2174/13816128113199990489.
Reprogramming of energy metabolism has recently been added to the list of hallmarks that define cancer. Cellular metabolism plays a central role in cancer initiation and progression to metastatic disease. Genotypic and phenotypic metabolic alterations are seen throughout tumourigenesis, allowing cancer cells to sustain increased rates of proliferation. Furthermore, this shift fuels necessary substrates for nucleotide, protein, and lipid synthesis to support cell growth. Beyond the 'Warburg effect', the widely observed increase in the glycolytic processing of glucose in cancer cells, numerous other metabolic changes have been characterized in cancer. Metabolomics provides a valuable platform for the investigation of the metabolic perturbations that occur in different disease states using a systems biology approach to determine metabolic profiles of biological samples. As cell metabolism is a complex network of interdependent pathways, local alterations will have an impact on overall tumor metabolism. In this review, we will highlight particular pathways, including glycolysis, nucleotide biosynthesis, lipid metabolism, and bioenergetics with an eye towards selected metabolic targets that may provide a novel approach to therapeutic development. Specific regulatory factors, including Myc, p53, HIF-1 and mTOR are briefly highlighted, as well as the key signaling pathways that can affect cellular metabolism. To demonstrate the powerful utility of high-throughput metabolite profiling techniques, we present a practical example of the metabolomic profiling of metastatic cells derived from a lung cancer metastasis model.
能量代谢重编程最近已被列入定义癌症的特征清单。细胞代谢在癌症的起始和向转移性疾病的进展中起着核心作用。在整个肿瘤发生过程中都能看到基因型和表型的代谢改变，这使得癌细胞能够维持更高的增殖率。此外，这种转变为核苷酸、蛋白质和脂质合成提供了必要的底物，以支持细胞生长。除了“瓦伯格效应”（即癌细胞中普遍观察到的葡萄糖糖酵解过程增加）之外，癌症中还发现了许多其他代谢变化。代谢组学提供了一个有价值的平台，用于使用系统生物学方法研究不同疾病状态下发生的代谢紊乱，以确定生物样品的代谢谱。由于细胞代谢是一个相互依赖途径的复杂网络，局部改变将对整体肿瘤代谢产生影响。在本综述中，我们将重点介绍特定的途径，包括糖酵解、核苷酸生物合成、脂质代谢和生物能量学，着眼于可能为治疗开发提供新方法的选定代谢靶点。简要强调了特定的调节因子，包括Myc、p53、HIF-1和mTOR，以及可能影响细胞代谢的关键信号通路。为了证明高通量代谢物谱分析技术的强大效用，我们展示了一个来自肺癌转移模型的转移细胞代谢组学分析的实际例子。
