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首页> 外文期刊>Current Biology: CB >Warburg Effect Metabolism Drives Neoplasia in a ce:italic>Drosophila/ce:italic> Genetic Model of Epithelial Cancer
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Warburg Effect Metabolism Drives Neoplasia in a ce:italic>Drosophila/ce:italic> Genetic Model of Epithelial Cancer

机译：Warburg效应新陈代谢在＆ ce：斜视＆ / ce：斜体>上皮癌的遗传模型

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摘要

Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formationin?vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in aDrosophilamodel. LDH is upregulated during the transition from hyperplasia to neoplasia, and neoplasia is prevented by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably, genetic alterations that increase glucose flux, or a high-sugar diet, are also sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We provide evidence that increased LDHA expression promotes a transformed phenotype in a human primary breast cell culture model. Furthermore, analysis of publically available cancer data showed evidence of synergy between elevated EGFR and LDHA activity linked to poor clinical outcome in a number of human cancers. Altered metabolism has generally been assumed to be an enabling feature that accelerates cancer cell proliferation. Our findings provide evidence that sugar metabolism may have a more profound role in driving neoplasia than previously appreciated.
机译：癌症在复杂的突变景观中发展。肿瘤形成的遗传模型已被用于探讨突变的组合如何合作，以促进肿瘤形成蛋白？体内。在此，我们鉴定乳酸脱氢酶（LDH），Warburg效应代谢的关键酶，作为表皮生长因子受体（EGFR） - 驱动的上皮瘤和在脂质醇中的转移的合作因子。 LDH在从增生到肿瘤的过渡期间上调，通过LDH耗尽来预防肿瘤。升高的LDH足以推动这种过渡。值得注意的是，增加葡萄糖通量或高糖饮食的遗传改变也足以促进EGFR驱动的肿瘤，这取决于LDH活性。我们提供了升高的LDHA表达促进人原发性乳腺细胞培养模型中的转化表型。此外，公开可用的癌症数据的分析显示了与许多人类癌症相关的临床结果相关的EGFR和LDHA活性之间的协同作用。通常假设改变的新陈代谢是一种加速癌细胞增殖的能够实现功能。我们的调查结果提供了证据表明糖代谢可能在驾驶肿瘤中具有比以前更受欢迎的更深刻的作用。

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