Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1
作者： A Fassl , K E Tagscherer , J Richter , M Berriel Diaz , S R Alcantara Llaguno
DOI: 10.1038/ONC.2011.615
关键词: Signal transduction 、 Cell biology 、 Tumor necrosis factor alpha 、 Growth factor receptor inhibitor 、 Neural stem cell 、 Epidermal growth factor receptor 、 Apoptosis 、 Biology 、 Growth factor receptor 、 Cell cycle
摘要: The Notch1-mediated signaling pathway has a central role in the maintenance of neural stem cells and contributes to growth progression glioblastomas, most frequent malignant brain tumors adults. Here, we demonstrate that Notch1 receptor promotes survival glioblastoma by regulation anti-apoptotic Mcl-1 protein. Notch1-dependent occurs cell type dependent at transcriptional or post-translational level is mediated induction epidermal factor (EGFR). Inhibition overcomes apoptosis resistance sensitizes induced ionizing radiation, death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) Bcl-2/Bcl-XL inhibitor ABT-737. In conclusion, targeting might represent promising novel strategy treatment glioblastomas.
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