Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production

Juan M. Funes, Marisol Quintero, Stephen Henderson, Dolores Martinez, Uzma Qureshi, Claire Westwood, Mark O. Clements, Dimitra Bourboulia, R. Barbara Pedley, Salvador Moncada, Chris Boshoff

    Research output: Contribution to journalArticlepeer-review


    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. © 2007 by The National Academy of Sciences of the USA.
    Original languageEnglish
    Pages (from-to)6223-6228
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number15
    Publication statusPublished - 10 Apr 2007


    • Adult stem cells
    • Glycolysis
    • Warburg effect


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