A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes
Copyright policy )A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes
In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jκ, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous inactivation of RBP-Jκ and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors.
- Helmholtz Association of German Research Centres Germany
- Cleveland Clinic United States
- University of Basel Switzerland
- Cleveland Clinic Lerner Research Institute United States
- University Hospital of Basel Switzerland
Cancer Research, Kaplan-Meier Estimate, Prosencephalon, Neural Stem Cells, Databases, Genetic, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Cell Proliferation, Mice, Knockout, Platelet-Derived Growth Factor, Brain Neoplasms, Gene Expression Profiling, Gene Transfer Techniques, Cell Biology, Glioma, Gene Expression Regulation, Neoplastic, Infusions, Intraventricular, Phenotype, Oncology, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Neoplastic Stem Cells, Neoplasm Grading
Cancer Research, Kaplan-Meier Estimate, Prosencephalon, Neural Stem Cells, Databases, Genetic, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Cell Proliferation, Mice, Knockout, Platelet-Derived Growth Factor, Brain Neoplasms, Gene Expression Profiling, Gene Transfer Techniques, Cell Biology, Glioma, Gene Expression Regulation, Neoplastic, Infusions, Intraventricular, Phenotype, Oncology, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Neoplastic Stem Cells, Neoplasm Grading
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