Research

Hippo pathway elements co-localize with occludin:a possible sensor system in pancreatic epithelial cells


Reference:

Santos Cravo, A., Mrsny, R., Carter, E., Harvey, E., Furutani-Seiki, M. and Erkan, M., 2015. Hippo pathway elements co-localize with occludin:a possible sensor system in pancreatic epithelial cells. Tissue Barriers, 3 (3), e1037948.

Related documents:

[img]
Preview
PDF (Accepted Manuscript) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (552kB) | Preview

    Official URL:

    http://dx.doi.org/10.1080/21688370.2015.1037948

    Abstract

    External adherens junction-based cell-cell contacts involving E-cadherin interactions function to sense planar cell status and modulate epithelial cell proliferation through Hippo (Hpo) and non-canonical Wnt pathways signaling. We hypothesized these regulatory processes should also be sensitive to a similar cell-cell contact sensor associated with apical-basal polarity events at epithelial surfaces. We used two human pancreatic cancer cell lines to explore this hypothesis: one with the capacity to form functional tight junction structures and polarize (HPAFII) and one lacking this capacity (AsPc1). Occludin (Ocln), a tetraspanning protein associated with TJ structures and capable of establishing external cell-cell contacts, was observed to partially co-localize with Hpo elements YAP (c-yes associated protein) and TEAD (TEA-dependent), which function to drive a proliferative transcription program. Treatment with dobutamine, known to affect YAP, was shown to suppress proliferation in an Ocln-dependent manner. Blockade of protein kinase C-zeta (PKC-ζ) diminished transepithelial electrical resistance (TER) of HPAFII monolayers that was not corrected by dobutamine treatment while the loss of TER resulting from inhibition of ROCK1 could be partially recovered. Examination of normal and cancerous human pancreatic biopsies showed that the cellular localization of Ocln, c-Yes, YAP, and TEAD were similar to HPAFII for normal cells and AsPc1 for cancerous cells. Together, these results suggest a link between Hpo and signals emanating from cell-cell contacts involving Ocln that may regulate pancreatic cell proliferation through the coordination of planar cell polarity with apical-basal polarity events.

    Details

    Item Type Articles
    CreatorsSantos Cravo, A., Mrsny, R., Carter, E., Harvey, E., Furutani-Seiki, M. and Erkan, M.
    DOI10.1080/21688370.2015.1037948
    Uncontrolled Keywordspancreatic cancer cells; dobutamine; tight junctions; occludin; yap.
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    Faculty of Science > Biology & Biochemistry
    Research CentresCentre for Regenerative Medicine
    Publisher StatementAccepted_Manuscript.pdf: This is an Accepted Manuscript of an article published by Taylor & Francis in Tissue Barriers on [date of publication], available online: http://wwww.tandfonline.com/10.1080/21688.70.2015.1037948
    RefereedYes
    StatusPublished
    ID Code44553

    Export

    Actions (login required)

    View Item

    Document Downloads

    More statistics for this item...