| Dose-Dependent Proteomic Analysis of Glioblastoma Cancer Stem Cells upon Treatment with Gamma-Secretase Inhibitor. | |
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MedLine Citation:
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PMID: 21932445 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Notch Signaling has been demonstrated to have a central role in Glioblastoma (GBM) Cancer Stem Cells (CSCs) and we have demonstrated recently that Notch pathway blockade by ã-secretase inhibitor (GSI) depletes GBM CSCs and prevents tumor propagation both in vitro and in vivo. In order to understand the proteome alterations involved in this transformation, a dose-dependent quantitative mass spectrometry (MS) based proteomic study has been performed based on global proteome profiling and a target verification phase where both Immunoassay and a Multiple Reaction Monitoring (MRM) assay are employed. The selection of putative protein candidates for confirmation poses a challenge due to the large number of identifications from the discovery phase. A multilevel filtering strategy together with literature mining is adopted to transmit the most confident candidates along the pipeline. Our results indicate that treating GBM CSCs with GSI induces a phenotype transformation towards non-tumorigenic cells with decreased proliferation and increased differentiation, as well as elevated apoptosis. Suppressed glucose metabolism and attenuated NFR2-mediated oxidative stress response are also suggested from our data, possibly due to their crosstalk with Notch Signaling. Overall, this quantitative proteomic based dose-dependent work complements our current understanding of the altered signaling events occurring upon the treatment of GSI in GBM CSCs. |
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Authors:
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Lan Dai; Jintang He; Yashu Liu; Jaeman Byun; Anuradha Vivekanandan; Subramaniam Pennathur; Xing Fan; David M Lubman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-19 |
Journal Detail:
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Title: Proteomics Volume: - ISSN: 1615-9861 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101092707 Medline TA: Proteomics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Program of Bioinformatics, University of Michigan Medical Center, Ann Arbor, MI, 48109. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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