The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation.
The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation.
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Warburg效应决定了丁酸酯介导的组蛋白乙酰化和细胞增殖的机制。
DOI：
10.1016/j.molcel.2012.08.033
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发表时间：
2012-11-30
期刊：
影响因子：
16
通讯作者：
Bultman, Scott J.
中科院分区：
文献类型：
--
作者：
Donohoe, Dallas R.;Collins, Leonard B.;Wali, Aminah;Bigler, Rebecca;Sun, Wei;Bultman, Scott J.
基因表达的广泛变化驱动肿瘤发生，但我们对癌细胞中异常表观基因组和转录组谱是如何产生的知之甚少。在这里，我们证明了代谢转化起着重要的作用。丁酸是正常结肠细胞的主要能量来源，并被代谢为乙酰辅酶A，这不仅对能量学而且对HAT活性都很重要。由于瓦尔堡效应，癌性结肠细胞依赖于葡萄糖作为其主要能量来源，因此丁酸盐积累并作为HDAC抑制剂发挥作用。虽然这两种机制增加组蛋白乙酰化，不同的靶基因上调。因此，当阻止发生瓦尔堡效应时，丁酸盐刺激正常结肠细胞和癌性结肠细胞的增殖，而丁酸盐抑制经历瓦尔堡效应的癌性结肠细胞的增殖。这些发现将一种常见的代谢物与表观遗传机制联系起来，这些机制因其固有的代谢差异而被正常细胞和癌细胞差异利用。
Widespread changes in gene expression drive tumorigenesis, yet our knowledge of how aberrant epigenomic and transcriptome profiles arise in cancer cells is poorly understood. Here, we demonstrate that metabolic transformation plays an important role. Butyrate is the primary energy source of normal colonocytes and is metabolized to acetyl-CoA, which was shown to be important not only for energetics but also for HAT activity. Due to the Warburg effect, cancerous colonocytes rely on glucose as their primary energy source so butyrate accumulated and functioned as an HDAC inhibitor. Although both mechanisms increased histone acetylation, different target genes were upregulated. Consequently, butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring, whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect. These findings link a common metabolite to epigenetic mechanisms that are differentially utilized by normal and cancerous cells because of their inherent metabolic differences.
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影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
DOI：
10.1111/j.1440-1746.2008.05490.x
发表时间：
2008-08-01
影响因子：
4.1
作者：
Balamurugan, Ramadass;Rajendiran, Ethendhar;Ramakrishna, Balakrishnan S.
通讯作者：
Ramakrishna, Balakrishnan S.
DOI：
10.1073/pnas.0504934102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Drusco, A;Zanesi, N;Croce, CM
通讯作者：
Croce, CM
影响因子：
4.2
作者：
Lupton, JR
通讯作者：
Lupton, JR
影响因子：
13.8
作者：
Guan, Kun-Liang;Xiong, Yue
通讯作者：
Xiong, Yue