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

Funes, J.M., Quintero, M., Henderson, S.R., Martinez, D., Qureshi, U., Westwood, C., Clements, M.O., Bourboulia, D., Pedley, R.B., Moncada, S. and Boshoff, C. 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. https://doi.org/10.1073/pnas.0700690104

TitleTransformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production
AuthorsFunes, J.M., Quintero, M., Henderson, S.R., Martinez, D., Qureshi, U., Westwood, C., Clements, M.O., Bourboulia, D., Pedley, R.B., Moncada, S. and Boshoff, C.
Abstract

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.

JournalProceedings of the National Academy of Sciences
Journal citation104 (15), pp. 6223-6228
ISSN0027-8424
Year10 Apr 2007
Digital Object Identifier (DOI)https://doi.org/10.1073/pnas.0700690104
Web address (URL)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851087/?tool=pubmed
Publication dates
Published10 Apr 2007

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