| Overlapping and divergent signalling pathways of N- and VE-cadherin in endothelial cells. | |
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MedLine Citation:
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PMID: 22246030 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Costanza Giampietro; Andrea Taddei; Monica Corada; Gian Maria Sarra-Ferraris; Myriam Alcalay; Ugo Cavallaro; Fabrizio Orsenigo; Maria Grazia Lampugnani; Elisabetta Dejana |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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FIRC Institute of Molecular Oncology, Milan, Italy; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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