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Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells
Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630302/ https://www.ncbi.nlm.nih.gov/pubmed/29029402 http://dx.doi.org/10.18632/oncotarget.18117 |
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author | Bayin, N. Sumru Frenster, Joshua D. Sen, Rajeev Si, Sheng Modrek, Aram S. Galifianakis, Nataliya Dolgalev, Igor Ortenzi, Valerio Illa-Bochaca, Irineu Khahera, Anadjeet Serrano, Jonathan Chiriboga, Luis Zagzag, David Golfinos, John G. Doyle, Werner Tsirigos, Aristotelis Heguy, Adriana Chesler, Mitch Barcellos-Hoff, Mary Helen Snuderl, Matija Placantonakis, Dimitris G. |
author_facet | Bayin, N. Sumru Frenster, Joshua D. Sen, Rajeev Si, Sheng Modrek, Aram S. Galifianakis, Nataliya Dolgalev, Igor Ortenzi, Valerio Illa-Bochaca, Irineu Khahera, Anadjeet Serrano, Jonathan Chiriboga, Luis Zagzag, David Golfinos, John G. Doyle, Werner Tsirigos, Aristotelis Heguy, Adriana Chesler, Mitch Barcellos-Hoff, Mary Helen Snuderl, Matija Placantonakis, Dimitris G. |
author_sort | Bayin, N. Sumru |
collection | PubMed |
description | Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch signaling, populate tumors regardless of local vascularity and selectively utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis and resistance to hypoxia. These findings demonstrate a novel role for Notch signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity ensures metabolic adaptations to support tumor growth in diverse tumor microenvironments. |
format | Online Article Text |
id | pubmed-5630302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56303022017-10-12 Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells Bayin, N. Sumru Frenster, Joshua D. Sen, Rajeev Si, Sheng Modrek, Aram S. Galifianakis, Nataliya Dolgalev, Igor Ortenzi, Valerio Illa-Bochaca, Irineu Khahera, Anadjeet Serrano, Jonathan Chiriboga, Luis Zagzag, David Golfinos, John G. Doyle, Werner Tsirigos, Aristotelis Heguy, Adriana Chesler, Mitch Barcellos-Hoff, Mary Helen Snuderl, Matija Placantonakis, Dimitris G. Oncotarget Research Paper Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch signaling, populate tumors regardless of local vascularity and selectively utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis and resistance to hypoxia. These findings demonstrate a novel role for Notch signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity ensures metabolic adaptations to support tumor growth in diverse tumor microenvironments. Impact Journals LLC 2017-05-23 /pmc/articles/PMC5630302/ /pubmed/29029402 http://dx.doi.org/10.18632/oncotarget.18117 Text en Copyright: © 2017 Bayin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bayin, N. Sumru Frenster, Joshua D. Sen, Rajeev Si, Sheng Modrek, Aram S. Galifianakis, Nataliya Dolgalev, Igor Ortenzi, Valerio Illa-Bochaca, Irineu Khahera, Anadjeet Serrano, Jonathan Chiriboga, Luis Zagzag, David Golfinos, John G. Doyle, Werner Tsirigos, Aristotelis Heguy, Adriana Chesler, Mitch Barcellos-Hoff, Mary Helen Snuderl, Matija Placantonakis, Dimitris G. Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title | Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title_full | Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title_fullStr | Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title_full_unstemmed | Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title_short | Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
title_sort | notch signaling regulates metabolic heterogeneity in glioblastoma stem cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630302/ https://www.ncbi.nlm.nih.gov/pubmed/29029402 http://dx.doi.org/10.18632/oncotarget.18117 |
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