Document Detail

Tumor cell invasiveness correlates with changes in integrin expression and localization.
MedLine Citation:
PMID:  15688013     Owner:  NLM     Status:  MEDLINE    
In nontumorigenic mammary epithelial cells (EpH4), transforming growth factor-beta (TGFbeta1) causes cell cycle arrest/apoptosis, but induces epitheliomesenchymal transition (EMT) in Ha-Ras-transformed EpH4 cells (EpRas). EMT is closely correlated with late-stage tumor progression and results in fibroblastic, migratory cells displaying a mesenchymal gene expression program (FibRas). EpRas and FibRas cells showed strongly increased cell substrate adhesion to fibronectin, collagens I/IV and laminin 1. Furthermore, Ras transformation caused enhanced or de-novo expression of the integrin subunits beta1, alpha2 and alpha3, or alpha5 and alpha6, respectively, the latter subunits being even more strongly expressed in FibRas cells. Importantly, polarized EpRas cells expressed integrin subunits beta1 and alpha6 at distinct (apical and lateral) membrane domains, while FibRas cells coexpressed these integrins and alpha5 at the entire plasma membrane. During EMT, EpRas cells formed an alpha5beta1 complex and deposited its ligand fibronectin into the extracellular matrix. Function-blocking alpha5 antibodies attenuated migration, and caused massive apoptosis in EpRas cells undergoing TGFbeta1-induced EMT in collagen gels, but failed to affect EpRas- or FibRas-derived structures. We conclude that functional alpha5beta1 integrin is centrally implicated in EMT induction. Importantly, FibRas cells also failed to deposit the alpha6beta4 ligand laminin 5, suggesting that alpha6beta4 is no longer functional after EMT and replaced by mesenchymal integrins such as alpha5beta1.
Sabine Maschler; Gerhard Wirl; Herbert Spring; Dorothea V Bredow; Isabelle Sordat; Hartmut Beug; Ernst Reichmann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-17     Completed Date:  2005-04-18     Revised Date:  2006-04-13    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2032-41     Citation Subset:  IM    
Research Institute of Molecular Pathology, Dr Bohrgasse 7, Vienna 1030, Austria.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism
Epithelial Cells / pathology,  physiology
Gene Expression Regulation, Neoplastic
Genes, ras
Integrins / genetics*
MAP Kinase Signaling System
Neoplasm Invasiveness / genetics*
Wound Healing / physiology
Reg. No./Substance:
0/Integrins; EC 3-Kinase

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