Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production
Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production
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DOI：
10.1073/pnas.0700690104
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发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Boshoff, Chris
中科院分区：
文献类型：
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作者：
Funes, Juan M.;Quintero, Marisol;Boshoff, Chris
对糖酵解产生ATP的依赖性增加被认为是肿瘤细胞的标志。这种糖酵解活性的增加是否主要是由于固有的代谢改变或缺氧微环境仍然存在争议。在这里，我们已经转化了人成体间充质干细胞（MSC）使用遗传改变所描述的分化细胞。我们的数据表明，MSC需要破坏与分化细胞相同的途径，以赋予完全转化的表型。此外，我们发现MSC比原代人成纤维细胞更糖酵解，并且与分化的细胞相反，在转化过程中不依赖于增加的有氧糖酵解来产生ATP。这些数据表明有氧糖酵解（瓦尔堡效应）不是成体干细胞转化的内在组成部分，并且在某些情况下，致癌适应生物能量需求也可能依赖于氧化磷酸化的增加。然而，我们确实发现，在由转化的MSC产生的肿瘤中，糖酵解酶的转录可逆增加，表明这是肿瘤适应其微环境的继发现象。
An increased dependency on glycolysis for ATP production is considered to be a hallmark of tumor cells. Whether this increase in glycolytic activity is due mainly to inherent metabolic alterations or to the hypoxic microenvironment remains controversial. Here we have transformed human adult mesenchymal stem cells (MSC) using genetic alterations as described for differentiated cells. Our data suggest that MSC require disruption of the same pathways as have been shown for differentiated cells to confer a fully transformed phenotype. Furthermore, we found that MSC are more glycolytic than primary human fibroblasts and, in contrast to differentiated cells, do not depend on increased aerobic glycolysis for ATP production during transformation. These data indicate that aerobic glycolysis (the Warburg effect) is not an intrinsic component of the transformation of adult stem cells, and that oncogenic adaptation to bioenergetic requirements, in some circumstances, may also rely on increases in oxidative phosphorylation. We did find, however, a reversible increase in the transcription of glycolytic enzymes in tumors generated by transformed MSC, indicating this is a secondary phenomenon resulting from adaptation of the tumor to its microenvironment.