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首页> 外文期刊>Cell metabolism >13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression.
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13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression.

机译：13 C-丙酮酸盐成像显示c-Myc诱导的肿瘤形成和消退之前糖酵解的改变。

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Tumor cells have an altered metabolic phenotype characterized by increased glycolysis and diminished oxidative phosphorylation. Despite the suspected importance of glycolysis in tumorigenesis, the temporal relationship between oncogene signaling, in vivo tumor formation, and glycolytic pathway activity is poorly understood. Moreover, how glycolytic pathways are altered as tumors regress remains unknown. Here, we use a switchable model of Myc-driven liver cancer, along with hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression. LDHA abundance and activity in tumors is tightly correlated to in vivo pyruvate conversion to lactate and is rapidly inhibited as tumors begin to regress, as are numerous glycolysis pathway genes. Conversion of pyruvate to alanine predominates in precancerous tissues prior to observable morphologic or histological changes. These results demonstrate that metabolic changes precede tumor formation and regression and are directly linked to the activity of a single oncogene.
机译：肿瘤细胞具有改变的代谢表型，其特征在于增加的糖酵解和减少的氧化磷酸化。尽管怀疑糖酵解在肿瘤发生中的重要性，但对癌基因信号传导，体内肿瘤形成和糖酵解途径活性之间的时间关系知之甚少。此外，糖酵解途径如何随着肿瘤的消退而改变仍然未知。在这里，我们使用Myc驱动的肝癌的可切换模型，以及超极化（13）C-丙酮酸磁共振波谱成像（MRSI），以可视化从头进行肿瘤形成和消退的糖酵解。肿瘤中LDHA的丰度和活性与体内丙酮酸转化为乳酸紧密相关，并且随着肿瘤开始消退而迅速被抑制，糖酵解途径基因也是如此。在可观察到的形态学或组织学变化之前，在癌前组织中丙酮酸向丙氨酸的转化占主导。这些结果表明，代谢变化先于肿瘤形成和消退，并且与单个癌基因的活性直接相关。

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