| Necrosis induction in glioblastoma cells reveals a new "bioswitch" function for the MT1-MMP/G6PT signaling axis in proMMP-2 activation versus cell death decision. | |
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MedLine Citation:
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PMID: 17460777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytoskeleton disorganization is an early step in the activation process of matrix metalloproteinase 2 (MMP-2) by membrane type 1 MMP (MT1-MMP) but is also associated with endoplasmic reticulum (ER) dysfunction and subsequent cell death. Given evidence that the ER-embedded glucose-6-phosphate transporter (G6PT) regulates glioblastoma cell survival and that MT1-MMP is a key enzyme in the cancer cell invasive phenotype, we explored the molecular link between G6PT and MT1-MMP. Cytoskeleton-disrupting agents such as concanavalin A (ConA) and cytochalasin D triggered proMMP-2 activation and cell death in U87 glioma cells. ConA decreased G6PT gene expression, an event that was also observed in cells overexpressing the full-length recombinant MT1-MMP protein. Overexpression of a membrane-bound catalytically active but cytoplasmic domain-deleted MT1-MMP was unable to downregulate G6PT gene expression or to trigger necrosis. Gene silencing of MT1-MMP with small interfering RNA prevented proMMP-2 activation and induced G6PT gene expression. ConA inhibited Akt phosphorylation, whereas overexpression of recombinant G6PT rescued the cells from ConA-induced proMMP-2 activation and increased Akt phosphorylation. Altogether, new functions of MT1-MMP in cell death signaling may be linked to those of G6PT. Our study indicates a molecular signaling axis regulating the invasive phenotype of brain tumor cells and highlights a new "bioswitch" function for G6PT in cell survival. |
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Authors:
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Anissa Belkaid; Simon Fortier; Jian Cao; Borhane Annabi |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neoplasia (New York, N.Y.) Volume: 9 ISSN: 1476-5586 ISO Abbreviation: Neoplasia Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-26 Completed Date: 2007-06-14 Revised Date: 2013-06-06 |
Medline Journal Info:
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Nlm Unique ID: 100886622 Medline TA: Neoplasia Country: Canada |
Other Details:
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Languages: eng Pagination: 332-40 Citation Subset: IM |
Affiliation:
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Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BIOMED, Université du Québec à Montréal, Quebec, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antiporters
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physiology* Brain Neoplasms / enzymology*, genetics, pathology* Cell Death / genetics Cell Line, Tumor Enzyme Activation / genetics Enzyme Precursors / genetics, metabolism* Gelatinases / genetics, metabolism* Glioblastoma / enzymology*, genetics, pathology* Humans Matrix Metalloproteinase 14 / genetics, physiology* Metalloendopeptidases / genetics, metabolism* Monosaccharide Transport Proteins / physiology* Necrosis Neoplasm Proteins / physiology Phenotype Signal Transduction* / genetics |
| Grant Support | |
ID/Acronym/Agency:
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1R01CA113553-01A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antiporters; 0/Enzyme Precursors; 0/Monosaccharide Transport Proteins; 0/Neoplasm Proteins; 0/SLC37A4 protein, human; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/progelatinase; EC 3.4.24.80/Matrix Metalloproteinase 14 |
| Comments/Corrections | |
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