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Overlapping and divergent signalling pathways of N- and VE-cadherin in endothelial cells.
MedLine Citation:
PMID:  22246030     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:  -    
Affiliation:
FIRC Institute of Molecular Oncology, Milan, Italy;
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