Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer.
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer.
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DOI：
10.1038/ncomms4128
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发表时间：
2014
影响因子：
16.6
通讯作者：
Mootha, Vamsi K.
中科院分区：
文献类型：
--
作者：
Nilsson, Roland;Jain, Mohit;Madhusudhan, Nikhil;Sheppard, Nina Gustafsson;Strittmatter, Laura;Kampf, Caroline;Huang, Jenny;Asplund, Anna;Mootha, Vamsi K.
代谢重塑现在被广泛认为是癌症的一个标志，但目前尚不清楚个体代谢策略是否经常被许多肿瘤利用。在这里，我们比较了跨越19种癌症类型的1,981个肿瘤中1,454个代谢酶的信使RNA图谱，以识别持续差异表达的酶。我们的荟萃分析恢复了一些最广泛使用的化疗药物的既定靶点，包括二氢叶酸还原酶、胸苷合成酶和核苷酸还原酶，同时也重点介绍了新的酶，如线粒体脯氨酸生物合成酶PYCR1。得分最高的途径是线粒体一碳代谢，以MTHFD2为中心。MTHFD2的RNA和蛋白在许多癌症中显著升高，并与乳腺癌的低生存率相关。MTHFD2在发育中的胚胎中有表达，但在大多数健康的成人组织中都不表达，即使是那些正在增殖的组织也是如此。我们的研究强调了癌症中单碳代谢的线粒体区划的重要性，并提出了重要的治疗假说。
Metabolic remodeling is now widely regarded as a hallmark of cancer, but it is not clear whether individual metabolic strategies are frequently exploited by many tumours. Here we compare messenger RNA profiles of 1,454 metabolic enzymes across 1,981 tumours spanning 19 cancer types to identify enzymes that are consistently differentially expressed. Our meta-analysis recovers established targets of some of the most widely used chemotherapeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while also spotlighting new enzymes, such as the mitochondrial proline biosynthetic enzyme PYCR1. The highest scoring pathway is mitochondrial one-carbon metabolism and is centred on MTHFD2. MTHFD2 RNA and protein are markedly elevated in many cancers and correlated with poor survival in breast cancer. MTHFD2 is expressed in the developing embryo, but is absent in most healthy adult tissues, even those that are proliferating. Our study highlights the importance of mitochondrial compartmentalization of one-carbon metabolism in cancer and raises important therapeutic hypotheses.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
7.4
作者：
Krishnan, Navasona;Dickman, Martin B.;Becker, Donald F.
通讯作者：
Becker, Donald F.
DOI：
10.1046/j.1432-1033.2003.03846.x
发表时间：
2003-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Hofbauer, KH;Gess, B;Kurtz, A
通讯作者：
Kurtz, A
影响因子：
9.3
作者：
Ben-Haim, Simona;Ell, Peter
通讯作者：
Ell, Peter
影响因子：
4.8
作者：
Patel, H;Di Pietro, E;MacKenzie, RE
通讯作者：
MacKenzie, RE