The Warburg effect: evolving interpretations of an established concept.
The Warburg effect: evolving interpretations of an established concept.
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Warburg效应：对既定概念的发展解释。
DOI：
10.1016/j.freeradbiomed.2014.08.027
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发表时间：
2015-02
影响因子：
7.4
通讯作者：
Wu, Shiyong
中科院分区：
文献类型：
--
作者：
Chen, Xiaozhuo;Qian, Yanrong;Wu, Shiyong
代谢重新编程和改变的生物能量学已经成为癌症的一个标志，也是活跃的基础和转化型癌症研究领域。在大多数癌症中，无论氧气供应如何，葡萄糖的运输和代谢都显著上调，这一现象被称为华宝效应，是这项研究的主要焦点之一。Warburg推测，由于线粒体氧化磷酸化(OXPHOS)的缺陷，即使在氧气存在的情况下，癌细胞也会切换到糖酵解来合成ATP。近十年的研究表明，虽然糖酵解确实在几乎所有的癌细胞中急剧上调，但线粒体的呼吸继续以与氧气供应成正比的速度正常运行。没有OXPHOS到糖酵解的转换，而是糖酵解的上调。此外，上调的糖酵解似乎是为了合成生物量和还原当量，除了产生ATP。大量糖酵解中间产物被转移到戊糖磷酸途径(PPP)以产生NADPH，这一新发现深刻地影响了癌细胞如何利用Warburg效应来应对活性氧物种(ROS)的产生和氧化应激，从而为利用这一点进行抗癌干预打开了大门。本文将对华宝效应及其与ROS和氧化应激控制的关系的最新发现进行综述。基于这些新发现的癌症治疗策略将被提出和讨论。
Metabolic reprogramming and altered bioenergetics have become emerged as a hallmark of cancer and an area of active basic and translational cancer research. Drastically upregulated glucose transport and metabolism in most cancers regardless the oxygen supply, a phenomenon called the Warburg effect, is one of major focuses of the research. Warburg speculated that cancer cells, due to defective mitochondrial oxidative phosphorylation (OXPHOS), switch to glycolysis for ATP synthesis, even in the presence of oxygen. Studies in the recent decade indicated that while glycolysis is indeed drastically upregulated in almost all cancer cells, mitochondrial respiration continues to operate normally at rates proportional to oxygen supply. There is no OXPHOS-to-glycolysis switch but rather upregulation of glycolysis. Furthermore, upregulated glycolysis appears to be for synthesis of biomass and reducing equivalents in addition to ATP production. The new finding that a significant amount of glycolytic intermediates are diverted to the pentose phosphate pathway (PPP) for production of NADPH has profound implications in how cancer cells use the Warburg effect to cope with reactive oxygen species (ROS) generation and oxidative stress, opening the door for anti-cancer interventions taking advantage of this. Recent findings in the Warburg effect and its relationship with ROS and oxidative stress controls will be reviewed. Cancer treatment strategies based on these new findings will be presented and discussed.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander
影响因子：
3.3
作者：
Amyere, M;Payrastre, B;Courtoy, PJ
通讯作者：
Courtoy, PJ
影响因子：
17.1
作者：
Chan DA;Sutphin PD;Nguyen P;Turcotte S;Lai EW;Banh A;Reynolds GE;Chi JT;Wu J;Solow-Cordero DE;Bonnet M;Flanagan JU;Bouley DM;Graves EE;Denny WA;Hay MP;Giaccia AJ
通讯作者：
Giaccia AJ