The emerging role and targetability of the TCA cycle in cancer metabolism.
The emerging role and targetability of the TCA cycle in cancer metabolism.
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DOI：
10.1007/s13238-017-0451-1
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发表时间：
2018-03
期刊：
影响因子：
21.1
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Anderson NM;Mucka P;Kern JG;Feng H
三羧酸（TCA）循环是细胞中氧化磷酸化的中心途径，并满足其生物能量，生物合成和氧化还原平衡的要求。尽管早期的教条认为癌细胞绕过TCA循环并主要利用有氧糖酵解，但新出现的证据表明某些癌细胞，特别是那些具有失调的癌基因和肿瘤抑制基因表达的癌细胞，严重依赖TCA循环来产生能量和合成大分子。随着该领域的进展，异常TCA循环功能在肿瘤发生中的重要性以及应用小分子抑制剂来扰乱增强的循环功能以用于癌症治疗的潜力开始发展。在这篇综述中，我们总结了目前的知识，燃料喂养的周期，致癌基因和肿瘤抑制因子对燃料和循环使用的影响，常见的遗传改变和失调的循环酶，以及潜在的治疗机会，针对癌细胞中的TCA循环。随着先进技术和体内模式生物研究的应用，我们希望对这个以前被忽视的生化中心的研究将为癌症代谢和肿瘤发生提供新的见解，随后揭示各种癌症类型的治疗干预的脆弱性。
The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.
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