| |  Online-Ressource |
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| Verfasst von: | Man, Ka-Hou [VerfasserIn]  |
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| | Wu, Yonghe [VerfasserIn] |
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| | Gao, Zhenjiang [VerfasserIn] |
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| | Spreng, Anna-Sophie [VerfasserIn] |
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| | Keding, Johanna [VerfasserIn] |
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| | Mangei, Jasmin [VerfasserIn] |
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| | Boskovic, Pavle [VerfasserIn] |
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| | Mallm, Jan-Philipp [VerfasserIn] |
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| | Liu, Hai-Kun [VerfasserIn] |
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| | Imbusch, Charles [VerfasserIn] |
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| | Lichter, Peter [VerfasserIn] |
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| | Radlwimmer, Bernhard [VerfasserIn] |
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| Titel: | SOX10 mediates glioblastoma cell-state plasticity |
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| Verf.angabe: | Ka-Hou Man, Yonghe Wu, Zhenjiang Gao, Anna-Sophie Spreng, Johanna Keding, Jasmin Mangei, Pavle Boskovic, Jan-Philipp Mallm, Hai-Kun Liu, Charles D Imbusch, Peter Lichter & Bernhard Radlwimmer |
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| E-Jahr: | 2024 |
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| Jahr: | 16 September 2024 |
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| Umfang: | 28 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 03.03.2025 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationEMBO reports |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2000 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 25(2024), 11, Seite 5113-5140 |
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| ISSN Quelle: | 1469-3178 |
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| Abstract: | Phenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis. |
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| DOI: | doi:10.1038/s44319-024-00258-8 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s44319-024-00258-8 |
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| | kostenfrei: Volltext: https://www.embopress.org/doi/full/10.1038/s44319-024-00258-8 |
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| | DOI: https://doi.org/10.1038/s44319-024-00258-8 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Glioblastoma |
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| | Phenotypic Plasticity |
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| | SOX10 |
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| | Therapy Resistance |
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| | Tumor Cell Quiescence |
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| K10plus-PPN: | 1918908338 |
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| Verknüpfungen: | → Zeitschrift |
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SOX10 mediates glioblastoma cell-state plasticity / Man, Ka-Hou [VerfasserIn]; 16 September 2024 (Online-Ressource)
