A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

被引：85

作者：

Giachino, Claudio ^{[1
]}

Boulay, Jean-Louis ^{[2
]}

Ivanek, Robert ^{[1
]}

Alvarado, Alvaro ^{[3
]}

Tostado, Cristobal ^{[2
]}

Lugert, Sebastian ^{[1
]}

Tchorz, Jan ^{[4
]}

Coban, Mustafa ^{[1
]}

Mariani, Luigi ^{[2
]}

Bettler, Bernhard ^{[4
]}

Lathia, Justin ^{[3
]}

Frank, Stephan ^{[5
]}

Pfister, Stefan ^{[6
]}

Kool, Marcel ^{[6
]}

Taylor, Verdon ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland

[2] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland

[3] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44195 USA

[4] Univ Basel, Dept Biomed, CH-4056 Basel, Switzerland

[5] Univ Basel, Inst Pathol, Div Neuropathol, CH-4031 Basel, Switzerland

[6] German Canc Res Ctr, Div Pediat Neurooncol, D-69121 Heidelberg, Germany

来源：

CANCER CELL | 2015年 / 28卷 / 06期

关键词：

NEURAL STEM-CELLS; NUCLEAR RECEPTOR TAILLESS; SELF-RENEWAL; GENOMIC ANALYSIS; BRAIN-TUMORS; GLIOMA; GLIOBLASTOMA; GROWTH; EXPRESSION; SURVIVAL;

D O I：

10.1016/j.ccell.2015.10.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-J kappa, 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-J kappa 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.

引用

页码：730 / 742

页数：13

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