• Login
    View Item 
    •   Home
    • Irish Health Organisations
    • Publications
    • View Item
    •   Home
    • Irish Health Organisations
    • Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Map of Submissions

    Home Page
    UlsterN
    5118
    UlsterS
    5118
    Connacht
    1710
    Munster
    58
    Leinster
    467

    Browse

    All of Lenus, The Irish Health RepositoryCommunitiesTitleAuthorsDate publishedSubjectsThis CollectionTitleAuthorsDate publishedSubjects

    My Account

    LoginRegister

    About

    About LenusDirectory of Open Access JournalsOpen Access Publishing GuideNational Health Library & Knowledge ServiceGuide to Publishers' PoliciesFAQsTerms and ConditionsVision StatementORCID Unique identifiers for ResearchersHSE position statement on Open AccessNational Open Research Forum (NORF)Zenodo (European Open Research repository)

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    bcr2853.xml
    Size:
    100.9Kb
    Format:
    XML
    Download
    Thumbnail
    Name:
    bcr2853.pdf
    Size:
    1.506Mb
    Format:
    PDF
    Download
    Thumbnail
    Name:
    BCR2853-S3.TIFF
    Size:
    111.0Kb
    Format:
    TIFF image
    Download
    Thumbnail
    Name:
    BCR2853-S1.TIFF
    Size:
    1.258Mb
    Format:
    TIFF image
    Download
    Thumbnail
    Name:
    BCR2853-S2.TIFF
    Size:
    996.4Kb
    Format:
    TIFF image
    Download
    View more filesView fewer files
    Authors
    McSherry, Elaine A
    Brennan, Kieran
    Hudson, Lance
    Hill, Arnold DK
    Hopkins, Ann M
    Issue Date
    2011-03-23
    
    Metadata
    Show full item record
    Citation
    Breast Cancer Research. 2011 Mar 23;13(2):R31
    URI
    http://hdl.handle.net/10147/127906
    Abstract
    Abstract Introduction The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. Methods MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and β1-integrin, we examined activation of the β1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and β1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. Results JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and β1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between JAM-A, AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. Conclusions Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.
    Item Type
    Journal Article
    Collections
    Publications

    entitlement

     
    Health Library Ireland | Health Service Executive | Jervis House, Jervis Street | Republic of Ireland | Eircode: D01 W596
    lenus@hse.ie | Tel: +353-1-7786275
    DSpace software copyright © 2002-2017  DuraSpace
    Contact Us | Disclaimer
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.