Inborn and acquired metabolic defects in cancer.
Inborn and acquired metabolic defects in cancer.
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DOI：
10.1007/s00109-011-0728-4
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发表时间：
2011-03
影响因子：
4.7
通讯作者：
Gottlieb, Eyal
中科院分区：
文献类型：
--
作者：
Frezza, Christian;Pollard, Patrick J.;Gottlieb, Eyal
奥托·瓦尔堡在大约世纪前就观察到新陈代谢的改变是癌症的根本原因。然而，随后对癌基因和抑癌基因的鉴定已经取代了瓦尔堡的理论，该理论指出遗传畸变是癌症的主要原因。然而，在过去的十年中，已经在编码三羧酸循环（TCA循环，也称为Krebs循环）和在细胞代谢中具有重要作用的密切相关的酶的基因中鉴定出癌症相关突变。这些观察结果重新唤起了人们对瓦尔堡假说的兴趣，并引发了一系列功能性研究，以期从机制上深入了解线粒体功能障碍、代谢改变和癌症之间的联系。在这篇综述中，我们讨论了一些TCA循环代谢物及其衍生物（肿瘤代谢物）的潜在促癌信号作用。特别是，我们专注于双加氧酶，一个家庭的氧和α-酮戊二酸依赖性的酶，控制，除其他事项外，缺氧诱导的转录因子的水平和活性和DNA和组蛋白脱甲基酶的活性的影响。
The observation that altered metabolism is the fundamental cause of cancer was made by Otto Warburg nearly a century ago. However, the subsequent identification of oncogenes and tumor suppressor genes has displaced Warburg's theory pointing towards genetic aberrations as the underlining cause of cancer. Nevertheless, in the last decade, cancer-associated mutations have been identified in genes coding for tricarboxylic acid cycle (TCA cycle, also known as Krebs cycle) and closely related enzymes that have essential roles in cellular metabolism. These observations have revived interest in Warburg's hypothesis and prompted a flurry of functional studies in the hope of gaining mechanistic insight into the links between mitochondrial dysfunction, metabolic alterations, and cancer. In this review, we discuss the potential pro-oncogenic signaling role of some TCA cycle metabolites and their derivatives (oncometabolites). In particular, we focus on their effects on dioxygenases, a family of oxygen and α-ketoglutarate-dependent enzymes that control, among other things, the levels and activity of the hypoxia-inducible transcription factors and the activity of DNA and histone demethylases.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
64.8
作者：
He, WH;Miao, FJP;Ling, L
通讯作者：
Ling, L
影响因子：
50.3
作者：
Lee, S;Nakamura, E;Schlisio, S
通讯作者：
Schlisio, S
影响因子：
51.1
作者：
Bayley, Jean-Pierre;Kunst, Henricus P. M.;Robledo, Mercedes
通讯作者：
Robledo, Mercedes