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解开脑癌中的代谢重编程之谜:利用质谱法发现关键分子靶点。

Untangling the Metabolic Reprogramming in Brain Cancer: Discovering Key Molecular Players Using Mass Spectrometry.

机构信息

Laboratory of Ion and Molecular Physics, Moscow Institute of Physics and Technology, Dolgoprudnyi, Russian Federation.

Federal State Autonomous Institution, N.N. Burdenko National Scientific and Practical Center for Neurosurgery of the Ministry of Healthcare of the Russian Feaderation, Moscow, Russian Federation.

出版信息

Curr Top Med Chem. 2019;19(17):1521-1534. doi: 10.2174/1568026619666190729154543.

Abstract

Cells metabolism alteration is the new hallmark of cancer, as well as an important method for carcinogenesis investigation. It is well known that the malignant cells switch to aerobic glycolysis pathway occurring also in healthy proliferating cells. Recently, it was shown that in malignant cells de novo synthesis of the intracellular fatty acid replaces dietary fatty acids which change the lipid composition of cancer cells noticeably. These alterations in energy metabolism and structural lipid production explain the high proliferation rate of malignant tissues. However, metabolic reprogramming affects not only lipid metabolism but many of the metabolic pathways in the cell. 2-hydroxyglutarate was considered as cancer cell biomarker and its presence is associated with oxidative stress influencing the mitochondria functions. Among the variety of metabolite detection methods, mass spectrometry stands out as the most effective method for simultaneous identification and quantification of the metabolites. As the metabolic reprogramming is tightly connected with epigenetics and signaling modifications, the evaluation of metabolite alterations in cells is a promising approach to investigate the carcinogenesis which is necessary for improving current diagnostic capabilities and therapeutic capabilities. In this paper, we overview recent studies on metabolic alteration and oncometabolites, especially concerning brain cancer and mass spectrometry approaches which are now in use for the investigation of the metabolic pathway.

摘要

细胞代谢改变是癌症的新标志,也是致癌研究的重要方法。众所周知,恶性细胞会转向有氧糖酵解途径,而这种途径也存在于健康增殖的细胞中。最近的研究表明,在恶性细胞中,内源性脂肪酸的从头合成取代了饮食中的脂肪酸,这使得癌细胞的脂质组成发生了明显的变化。这些能量代谢和结构脂质产生的改变解释了恶性组织的高增殖率。然而,代谢重编程不仅影响脂质代谢,还影响细胞内许多代谢途径。2-羟戊二酸被认为是癌细胞的生物标志物,其存在与影响线粒体功能的氧化应激有关。在各种代谢物检测方法中,质谱法作为同时鉴定和定量代谢物的最有效方法脱颖而出。由于代谢重编程与表观遗传学和信号转导修饰密切相关,因此评估细胞代谢物的改变是一种很有前途的研究致癌作用的方法,这对于提高当前的诊断能力和治疗能力是必要的。本文综述了近年来关于代谢改变和致癌代谢物的研究进展,特别是涉及脑癌和目前用于代谢途径研究的质谱方法。

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