Document Detail

Overlapping and divergent signalling pathways of N- and VE-cadherin in endothelial cells.
MedLine Citation:
PMID:  22246030     Owner:  NLM     Status:  Publisher    
Endothelial cells (ECs) express two members of the cadherin family, VE- and N-cadherin. While VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE- or N-cadherin leads to early foetal lethality suggesting that these cadherins play a non-redundant role in vascular development. We report here that VE-cadherin negatively controls junctional localization and expression of N-cadherin by limiting p120-catenin availability and reducing β-catenin transcriptional activity. Using EC lines expressing either VE- or N-cadherin we found that both cadherins inhibit cell proliferation and apoptosis. Both trigger the phosphatidylinositol-3-OH-kinase (PI3K)-AKT-Forkhead-box protein-O1 (FoxO1) pathway and reduce β-catenin transcriptional activity. The extent of signalling correlates with the total level of cadherins regardless of the type of cadherin expressed. In contrast, basal and Fibroblast Growth Factor (FGF)-induced cell motility is promoted by N-cadherin and strongly inhibited by VE-cadherin. This opposite effect is partly due to the ability of VE-cadherin to associate with FGF receptor and the Density-Enhanced Phosphatase-1 (Dep-1) which, in turn, inhibits receptor signalling. We conclude that VE- and N-cadherin have both additive and divergent effects on ECs. Differences in signalling are due, in part, to cadherin association with growth factor receptors and modulation of their downstream signalling.
Costanza Giampietro; Andrea Taddei; Monica Corada; Gian Maria Sarra-Ferraris; Myriam Alcalay; Ugo Cavallaro; Fabrizio Orsenigo; Maria Grazia Lampugnani; Elisabetta Dejana
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-12
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
FIRC Institute of Molecular Oncology, Milan, Italy;
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