TY  - JOUR
AU  - Giachino, Claudio
AU  - Boulay, Jean-Louis
AU  - Ivanek, Robert
AU  - Alvarado, Alvaro
AU  - Tostado, Cristobal
AU  - Lugert, Sebastian
AU  - Tchorz, Jan
AU  - Coban, Mustafa
AU  - Mariani, Luigi
AU  - Bettler, Bernhard
AU  - Lathia, Justin
AU  - Frank, Stephan
AU  - Pfister, Stefan
AU  - Kool, Marcel
AU  - Taylor, Verdon
TI  - A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes.
JO  - Cancer cell
VL  - 28
IS  - 6
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-02613
SP  - 730 - 742
PY  - 2015
AB  - 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.
KW  - Basic Helix-Loop-Helix Transcription Factors (NLM Chemicals)
KW  - Hes5 protein, mouse (NLM Chemicals)
KW  - Immunoglobulin J Recombination Signal Sequence-Binding Protein (NLM Chemicals)
KW  - Notch1 protein, mouse (NLM Chemicals)
KW  - Notch2 protein, mouse (NLM Chemicals)
KW  - Platelet-Derived Growth Factor (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-sis (NLM Chemicals)
KW  - Rbpj protein, mouse (NLM Chemicals)
KW  - Receptor, Notch1 (NLM Chemicals)
KW  - Receptor, Notch2 (NLM Chemicals)
KW  - Receptors, Notch (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
KW  - Tumor Suppressor Proteins (NLM Chemicals)
KW  - platelet-derived growth factor A (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26669487
DO  - DOI:10.1016/j.ccell.2015.10.008
UR  - https://inrepo02.dkfz.de/record/126585
ER  -