Document Detail


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.
MedLine Citation:
PMID:  17460777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anissa Belkaid; Simon Fortier; Jian Cao; Borhane Annabi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  9     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-26     Completed Date:  2007-06-14     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  332-40     Citation Subset:  IM    
Affiliation:
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BIOMED, Université du Québec à Montréal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Antiporters / 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:
1R01CA113553-01A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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