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Publication : A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes.

First Author  Giachino C Year  2015
Journal  Cancer Cell Volume  28
Issue  6 Pages  730-742
PubMed ID  26669487 Mgi Jnum  J:227329
Mgi Id  MGI:5700245 Doi  10.1016/j.ccell.2015.10.008
Citation  Giachino C, et al. (2015) A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes. Cancer Cell 28(6):730-42
abstractText  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-Jkappa, 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-Jkappa 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.
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