Document Detail


Defective cell migration in an ovarian cancer cell line is associated with impaired urokinase-induced tyrosine phosphorylation.
MedLine Citation:
PMID:  9271229     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The urokinase receptor (u-PAR), a protein anchored to cell membrane by a glycosyl phosphatidylinositol, plays a central role in cancer cell invasion and metastasis by binding urokinase plasminogen activator (u-PA), thereby facilitating plasminogen activation. Plasmin can promote cell migration either directly or by activating metalloproteinases that degrade some of the components of the extra cellular matrix. However, the IGR-OV1-Adria cell line contains the u-PAR but does not migrate even in the presence of exogenous u-PA, although the parental IGR-OV1 cell line migrates normally in the presence of u-PA. We therefore investigated the role of cell signalling for u-PA induced cell locomotion. We show that cell migration induced by u-PA-u-PAR complex is always associated with tyrosine kinase activation for the following reasons: (1) the blockade of the u-PAR by a chimeric molecule (albumin-ATF) inhibits not only the u-PA-induced cell migration, but also the signalling in IGR-OV1 line; (2) the binding of u-PA to u-PAR on non-migrating IGR-OV1-Adria cells was not associated with tyrosine kinase activation; (3) the inhibition of tyrosine kinase also blocked cell migration of IGR-OV1. Therefore tyrosine kinase activation seems to be essential for the u-PA-induced cell locomotion possibly by the formation of a complex u-PAR-u-PA with a protein whose transmembrane domain can ensure cell signalling. Thus, IGR-OV1 and IGR-OV1-Adria cell lines represent a good model for the analysis of the mechanism of u-PA-u-PAR-induced cell locomotion.
Authors:
S S Mirshahi; K C Lounes; H Lu; E Pujade-Lauraine; Z Mishal; J Bénard; A Bernadou; C Soria; J Soria
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  411     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-09-23     Completed Date:  1997-09-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  322-6     Citation Subset:  IM    
Affiliation:
Laboratoire Sainte Marie, Hôtel Dieu, Parvis de Notre Dame, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Movement / drug effects,  physiology*
Enzyme-Linked Immunosorbent Assay
Female
Fibrinolysin / metabolism
Glycosylphosphatidylinositols / physiology
Humans
Immunohistochemistry
Microscopy, Confocal
Ovarian Neoplasms
Phosphorylation
Phosphotyrosine / metabolism*
Plasminogen Activator Inhibitor 1 / analysis
Receptors, Cell Surface / metabolism*
Receptors, Urokinase Plasminogen Activator
Signal Transduction
Tumor Cells, Cultured
Urokinase-Type Plasminogen Activator / metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Glycosylphosphatidylinositols; 0/PLAUR protein, human; 0/Plasminogen Activator Inhibitor 1; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; 21820-51-9/Phosphotyrosine; EC 3.4.21.7/Fibrinolysin; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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


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