2026-06-14T05:06:41Zhttps://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
Repisalud author 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 funder Wellcome Trust 2024-02-01T11:43:42Z 2024-02-01T11:43:42Z 2007-04-10 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 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. eng Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production. journal article 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 URL https://repisalud.isciii.es/bitstreams/22620aed-8090-487a-b9ab-3de983cabe7c/download File MD5 9e19bf48d3eb2cf26e261a4a9f21e5bf 927414 application/pdf trasnformationofhuman-2007.pdf URL https://repisalud.isciii.es/bitstreams/5a8c4bcd-33cb-4794-bac5-d11b3cd36ccd/download File MD5 9848d40578c799d32c9818c8267931a3 259295 application/pdf 00690fig6.pdf URL https://repisalud.isciii.es/bitstreams/451cba22-d0b6-4c0f-94b9-85be2b0e48a7/download File MD5 1df07f8dbb4f2ab34b0b7ae2e5be43a5 312752 application/pdf 00690fig7.pdf URL https://repisalud.isciii.es/bitstreams/8fb08380-1e02-4b3e-94d2-6001ac01ce7e/download File MD5 92118e1617529b991f944fc63274060e 2366529 application/pdf 00690fig8.pdf URL https://repisalud.isciii.es/bitstreams/7dd728ca-26b3-47fd-8c7f-a1e7ff455aa4/download File MD5 8553e8af0b435af1d05cf66062503062 451471 application/pdf 00690fig9.pdf URL https://repisalud.isciii.es/bitstreams/74d93b44-2e1b-4d99-8f91-029822b203a4/download File MD5 388b8eaf7ee0c8c3bf990054160cc760 828357 application/pdf 00690fig10.pdf URL https://repisalud.isciii.es/bitstreams/498f14ef-fbfb-413e-bb3f-bd8d4a03da62/download File MD5 994f14be0ab25b4cb4e052aec33210bf 37228 text/plain trasnformationofhuman-2007.pdf.txt URL https://repisalud.isciii.es/bitstreams/f9635f1f-d1dd-4bea-8bfd-6943f4e093fb/download File MD5 33b51aef6d079c4205ea0d6de4fb9a99 286 text/plain 00690fig6.pdf.txt URL https://repisalud.isciii.es/bitstreams/82855ee6-2426-4acf-b155-0828b80ede8e/download File MD5 74c6fa8e4833c6e1f6ee5d7e1a345e5f 711 text/plain 00690fig7.pdf.txt URL https://repisalud.isciii.es/bitstreams/d375535b-6e99-4068-bdb0-c4a6ee5574a2/download File MD5 ed4957946271e33387333e1d934d5220 232 text/plain 00690fig8.pdf.txt URL https://repisalud.isciii.es/bitstreams/47d808ba-dd74-4e05-b7ab-529804349edf/download File MD5 35eb363a5d67f106683f0be5bbce67a1 2986 text/plain 00690fig9.pdf.txt URL https://repisalud.isciii.es/bitstreams/7ed38fb9-e2a2-4bc0-a6cb-5a247b4cd375/download File MD5 d0db9c867c51768ed5d9171d1e05d242 128 text/plain 00690fig10.pdf.txt