MYC-induced cancer cell energy metabolism and therapeutic opportunities.
MYC-induced cancer cell energy metabolism and therapeutic opportunities.
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DOI：
10.1158/1078-0432.ccr-09-0889
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Gao P
中科院分区：
文献类型：
--
作者：
Dang CV;Le A;Gao P
尽管癌症改变了葡萄糖代谢（称为瓦尔堡效应），即在足够的氧张力下癌细胞对葡萄糖的摄取和转化增加，但谷氨酰胺和脂肪酸代谢的变化也已被记录。 MYC 癌基因有助于许多人类癌症的发生，它编码一种转录因子 c-Myc，将细胞代谢的改变与肿瘤发生联系起来。 c-Myc 调节参与核糖体和线粒体生物发生以及葡萄糖和谷氨酰胺代谢调节的基因。对于 E2F1，c-Myc 诱导参与核苷酸代谢和 DNA 复制的基因，以及稳态减弱 E2F1 表达的 microRNA。异位 c-Myc 与缺氧诱导转录因子 HIF-1 协同诱导缺氧适应的转录程序。 Myc 直接调节基因表达，例如包括乳酸脱氢酶 A (LDHA) 在内的糖酵解基因，或间接调节基因表达，例如抑制 microRNA miR-23a/b 以增加谷氨酰胺酶 (GLS) 蛋白表达和谷氨酰胺代谢。因此，癌症中的异位 MYC 表达可以同时驱动有氧糖酵解和/或氧化磷酸化，为肿瘤微环境中的细胞生长和增殖提供足够的能量和合成代谢底物。总的来说，这些研究表明 Myc 介导的癌细胞能量代谢改变可以转化为新抗癌疗法的开发。
Although cancers have altered glucose metabolism, termed the Warburg effect that describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor, c-Myc, that links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anti-cancer therapies.