2026-06-14T03:40:14Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/174082024-11-29T18:49:59Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Funes, Juan M author Quintero, Marisol author Henderson, Stephen author Martinez Garcia, Maria Dolores author Qureshi, Uzma author Westwood, Claire author Clements, Mark O author Bourboulia, Dimitra author Pedley, R Barbara author Moncada, Salvador author Boshoff, Chris author 2007-04-10 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. Proc Natl Acad Sci U S A . 2007;104(15):6223-8. 10.1073/pnas.0700690104 0027-8424 Proceedings of the National Academy of Sciences of the United States of America 17384149 http://hdl.handle.net/20.500.12105/17408 Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production.