| Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1. | |
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MedLine Citation:
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PMID: 22249262 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The Notch1-mediated signaling pathway has a central role in the maintenance of neural stem cells and contributes to growth and progression of glioblastomas, the most frequent malignant brain tumors in adults. Here, we demonstrate that the Notch1 receptor promotes survival of glioblastoma cells by regulation of the anti-apoptotic Mcl-1 protein. Notch1-dependent regulation of Mcl-1 occurs cell type dependent at a transcriptional or post-translational level and is mediated by the induction of epidermal growth factor receptor (EGFR). Inhibition of the Notch1 pathway overcomes apoptosis resistance and sensitizes glioblastoma cells to apoptosis induced by ionizing radiation, the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) or the Bcl-2/Bcl-XL inhibitor ABT-737. In conclusion, targeting Notch1 might represent a promising novel strategy in the treatment of glioblastomas.Oncogene advance online publication, 16 January 2012; doi:10.1038/onc.2011.615. |
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Authors:
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A Fassl; K E Tagscherer; J Richter; M Berriel Diaz; S R Alcantara Llaguno; B Campos; J Kopitz; C Herold-Mende; S Herzig; M H H Schmidt; L F Parada; O D Wiestler; W Roth |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-16 |
Journal Detail:
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Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Molecular Tumor Pathology, DKFZ, Heidelberg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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