Regulation of glycolysis and the Warburg effect by estrogen-related receptors.
Regulation of glycolysis and the Warburg effect by estrogen-related receptors.
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雌激素相关受体对糖酵解及瓦博格效应的调控
DOI：
10.1038/onc.2012.221
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发表时间：
2013-04-18
期刊：
影响因子：
8
通讯作者：
Lu, J.
中科院分区：
文献类型：
--
作者：
Cai, Q.;Lin, T.;Kamarajugadda, S.;Lu, J.
癌细胞通常表现出改变的葡萄糖代谢，其特征在于有氧糖酵解的偏好，称为瓦尔堡效应，其促进细胞增殖。缺氧诱导因子（HIF）和癌蛋白Myc是两个重要的促进糖酵解的转录因子。以前我们报道了雌激素相关受体（ERRs）作为HIF的辅因子，在缺氧条件下增强糖酵解基因的HIF依赖性转录。ERR是孤儿核受体，通过协调线粒体生物合成、脂肪酸氧化（FAO）和氧化磷酸化（OXPHOS）来调节能量代谢。在这里，我们表明，ERRs也刺激糖酵解下常氧。ERR直接结合并激活许多编码糖酵解酶的基因的启动子，并且这些启动子中的ERR结合位点对于ERR介导的转录激活是必需的。ERRs与Myc相互作用，这两种因子协同激活糖酵解基因的转录。此外，ERRs的过表达增加糖酵解基因表达和乳酸产生。相反，癌细胞中ERRs的缺失降低了糖酵解基因的表达和葡萄糖摄取，导致有氧糖酵解和细胞生长减少。综上所述，这些结果表明，ERRs是糖酵解途径的重要转录激活因子，并有助于癌细胞中的瓦尔堡效应。
Cancer cells typically display altered glucose metabolism characterized by a preference of aerobic glycolysis, known as the Warburg effect, which facilitates cell proliferation. Hypoxia-inducible factor (HIF) and oncoprotein Myc are two prominent transcription factors that drive glycolysis. Previously we reported that the estrogen-related receptors (ERRs) act as cofactors of HIF and enhance HIF-dependent transcription of glycolytic genes under hypoxia. ERRs are orphan nuclear receptors and key regulators of energy metabolism by orchestrating mitochondrial biogenesis, fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS). Here we show that ERRs also stimulate glycolysis under normoxia. ERRs directly bind to and activate promoters of many genes encoding glycolytic enzymes, and the ERR-binding sites in such promoters are essential for ERR-mediated transcriptional activation. ERRs interact with Myc, and the two factors synergistically activate transcription of glycolytic genes. Furthermore, overexpression of ERRs increases glycolytic gene expression and lactate production. Conversely, depletion of ERRs in cancer cells reduces expression of glycolytic genes and glucose uptake, resulting in decreased aerobic glycolysis and cell growth. Taken together, these results suggest that ERRs are important transcriptional activators of the glycolytic pathway and contribute to the Warburg effect in cancer cells.
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影响因子：
5.3
作者：
Kim, JW;Zeller, KI;Dang, CV
通讯作者：
Dang, CV
影响因子：
64.8
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Sabatini, David M.
影响因子：
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作者：
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Sabatini, David M.
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影响因子：
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作者：
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通讯作者：
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