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Notch signaling as a tumor suppressor in glioma
Third-party funded project |
Project title |
Notch signaling as a tumor suppressor in glioma |
Principal Investigator(s) |
Taylor, Verdon
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Co-Investigator(s) |
Giachino, Claudio
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Organisation / Research unit |
Departement Biomedizin / Embryology and Stem Cell Biology (Taylor) |
Project start |
01.01.2015 |
Probable end |
31.12.2015 |
Status |
Completed |
Abstract |
Gliomas are aggressive brain cancers with limited therapeutic options and poor prognosis for patients. Genetic analysis has uncovered changes and mutations in a number of signaling pathways and intracellular pathway modulators. Although it remains controversial, neural stem and progenitor cells in the postnatal brain are believed to be one origin of gliomas. Notch signaling is required for neural stem cell (NSC) maintenance, promoting quiescence and blocking differentiation. Accordingly, Notch signaling promotes a self-renewing stem cell-like state in glioma cells. However, whether glioma initiation from NSCs or progenitor cells and tumor progression depend on Notch signaling has not been demonstrated. The proposed project will address the cell autonomous role of canonical Notch signaling in glioma cell biology using conditional genetics in multiple mouse models. We found that genetic deletion of RBPjk, the indispensable mediator of the canonical Notch signaling, in NSCs and progenitors does not impair platelet-derived growth factor-driven glioma growth but surprisingly accelerates tumor formation in mice. We will test the hypothesis that RBPjk cooperates with known tumor suppressors to control NSC proliferation, and loss of RBPjk and canonical Notch signaling promotes a premalignant state. We will also test the response of Notch signaling-deficient gliomas to standard Temozolomide chemotherapy. Our findings may uncover fundamental differences in the molecular requirements of NSCs versus glioma cells, possibly leading to the identification of targets for therapeutic intervention through combinatorial drug treatment. |
Financed by |
Foundations and Associations
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Published results () |
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ID |
Autor(en) |
Titel |
ISSN / ISBN |
Erschienen in |
Art der Publikation |
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3828978 |
Giachino, C.; Boulay, J. L.; Ivanek, R.; Alvarado, A.; Tostado, C.; Lugert, S.; Tchorz, J.; Coban, M.; Mariani, L.; Bettler, B.; Lathia, J.; Frank, S.; Pfister, S.; Kool, M.; Taylor, V. |
A tumor suppressor function for Notch signaling in forebrain tumor subtypes |
1535-6108 ; 1878-3686 |
Cancer Cell |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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08/05/2024
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