Differential profiling studies of N-linked glycoproteins in glioblastoma cancer stem cells upon treatment with γ-secretase inhibitor

We have recently demonstrated that Notch pathway blockade by γ‐secretase inhibitor (GSI) depletes cancer stem cells (CSCs) in Glioblastoma Multiforme (GBM) through reduced proliferation and induced apoptosis. However, the detailed mechanism by which the manipulation of Notch signal induces alteratio...

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Bibliographic Details
Published in:Proteomics (Weinheim) 2011-10, Vol.11 (20), p.4021-4028
Main Authors: Dai, Lan, Liu, Yashu, He, Jintang, Flack, Callie G., Talsma, Caroline E., Crowley, Jessica G., Muraszko, Karin M., Fan, Xing, Lubman, David M.
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases - antagonists & inhibitors
Blotting, Western
Cancer stem cells
Enzyme Inhibitors - pharmacology
Gene Expression Profiling
Gliobastoma
Glioblastoma
Glycoproteins - chemistry
Glycoproteomics
Humans
Label-free
Lectin microarray
Lectins - chemistry
Multi-lectin chromatography
Neoplastic Stem Cells - cytology
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Protein Array Analysis
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Summary:We have recently demonstrated that Notch pathway blockade by γ‐secretase inhibitor (GSI) depletes cancer stem cells (CSCs) in Glioblastoma Multiforme (GBM) through reduced proliferation and induced apoptosis. However, the detailed mechanism by which the manipulation of Notch signal induces alterations on post‐translational modifications such as glycosylation has not been investigated. Herein, we present a differential profiling work to detect the change of glycosylation pattern upon drug treatment in GBM CSCs. Rapid screening of differential cell surface glycan structures has been performed by lectin microarray on live cells followed by the detection of N‐linked glycoproteins from cell lysates using multi‐lectin chromatography and label‐free quantitative mass spectrometry analysis. A total of 51 and 52 glycoproteins were identified in the CSC‐ and GSI‐treated groups, respectively, filtered by a combination of decoy database searching and Trans‐Proteomic Pipeline (TPP) processing. Although no significant changes were detected from the lectin microarray experiment, 7 differentially expressed glycoproteins with high confidence were captured after the multi‐lectin column including key enzymes involved in glycan processing. Functional annotations of the altered glycoproteins suggest a phenotype transformation of CSCs toward a less tumorigenic form upon GSI treatment.
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.201100014