期刊
PROTEOMICS
卷 11, 期 23, 页码 4529-4540出版社
WILEY
DOI: 10.1002/pmic.201000730
关键词
Cancer stem cells; Cell Biology; Glioblastoma; Label-free; Multiple reaction monitoring; Pathway analysis
资金
- National Institute of Health [R01 49500, R21 CA134623]
- NIDDK, Molecular Phenotyping Core, Michigan Nutrition and Obesity Center [DK089503]
- Doris Duke Foundation
- Accelerate Brain Cancer Cure Project Award
- American Brain Tumor Association
- Voices Against Brain Cancer Research Grant
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 gamma-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 the 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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