Ras-dependent carbon metabolism and transformation in mouse broblasts
Ras-dependent carbon metabolism and transformation in mouse broblasts
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DOI：
10.1038/sj.onc.1209528
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发表时间：
2006-08-01
期刊：
影响因子：
8
通讯作者：
Alberghina, L.
中科院分区：
文献类型：
--
作者：
Chiaradonna, F.;Sacco, E.;Alberghina, L.
ras基因的突变激活对于不同恶性肿瘤的发生和维持是必需的。在这里，我们表明，使用分子生理学，营养扰动和转录前体的组合。令人惊讶的是，与致癌Ras激活相关的表型的完全外显率，包括碳代谢向发酵的转变和关键细胞周期调节因子的上调，取决于葡萄糖的可用性。这些反应是由Ras激活诱导的，通过显性负Ras特异性鸟嘌呤核苷酸交换蛋白的表达获得的Ras途径的下调而特异性逆转。我们的数据可以直接链接到ras激活癌细胞的能量代谢的改变，他们对葡萄糖短缺的脆弱性和随之而来的凋亡死亡。
Mutational activation of ras genes is required for the onset and maintenance of different malignancies. Here we show, using a combination of molecular physiology, nutritional perturbations and transcriptional pro. ling, that full penetrance of phenotypes related to oncogenic Ras activation, including the shift of carbon metabolism towards fermentation and upregulation of key cell cycle regulators, is dependent upon glucose availability. These responses are induced by Ras activation, being specifically reverted by downregulation of the Ras pathway obtained through the expression of a dominant-negative Ras-specific guanine nucleotide exchange protein. Our data allow to link directly to ras activation the alteration in energy metabolism of cancer cells, their fragility towards glucose shortage and ensuing apoptotic death.