Funes, Juan M. and Quintero, Marisol and Henderson, Stephen R. and Martinez, Dolores and Qureshi, Uzma and Westwood, Claire and Clements, Mark O. and Bourboulia, Dimitra and Pedley, R. Barbara and Moncada, Salvador and Boshoff, Chris (2007) Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production. Proceedings of the National Academy of Sciences, 104 (15). pp. 6223-6228. ISSN 0027-8424Full text not available from this repository.
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. Copyright (2007), National Academy of Sciences, U.S.A.
|Additional Information:||Online ISSN 1091-6490|
|Subjects:||University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)|
|Depositing User:||Miss Nina Watts|
|Date Deposited:||17 Jul 2007|
|Last Modified:||02 Feb 2010 09:17|
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