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

Ana Santos Cravo, Randy Mrsny, Edward Carter, Emma Harvey, Makoto Furutani-Seiki, Mert Erkan

Research output: Contribution to journalArticle

  • 3 Citations

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.

LanguageEnglish
Article numbere1037948
Pages1-35
Number of pages35
JournalTissue Barriers
Volume3
Issue number3
Early online date27 Mar 2015
DOIs
StatusPublished - 2015

Fingerprint

Occludin
Epithelial Cells
Acoustic impedance
Dobutamine
Proto-Oncogene Proteins c-yes
Sensors
Cell proliferation
Proteins
Contact sensors
Biopsy
Cadherins
Transcription
Monolayers
Cells
Electric Impedance
Cell Proliferation
Adherens Junctions
Cell Polarity
Wnt Signaling Pathway
Tight Junctions

Keywords

  • Pancreatic cancer cells; Dobutamine; Tight Junctions; Occludin; YAP.

Cite this

Hippo pathway elements co-localize with occludin : a possible sensor system in pancreatic epithelial cells. / Santos Cravo, Ana; Mrsny, Randy; Carter, Edward; Harvey, Emma; Furutani-Seiki, Makoto; Erkan, Mert.

In: Tissue Barriers, Vol. 3, No. 3, e1037948, 2015, p. 1-35.

Research output: Contribution to journalArticle

Santos Cravo, A, Mrsny, R, Carter, E, Harvey, E, Furutani-Seiki, M & Erkan, M 2015, 'Hippo pathway elements co-localize with occludin: a possible sensor system in pancreatic epithelial cells' Tissue Barriers, vol. 3, no. 3, e1037948, pp. 1-35. DOI: 10.1080/21688370.2015.1037948
Santos Cravo A, Mrsny R, Carter E, Harvey E, Furutani-Seiki M, Erkan M. Hippo pathway elements co-localize with occludin: a possible sensor system in pancreatic epithelial cells. Tissue Barriers. 2015;3(3):1-35. e1037948. Available from, DOI: 10.1080/21688370.2015.1037948
Santos Cravo, Ana ; Mrsny, Randy ; Carter, Edward ; Harvey, Emma ; Furutani-Seiki, Makoto ; Erkan, Mert. / Hippo pathway elements co-localize with occludin : a possible sensor system in pancreatic epithelial cells. In: Tissue Barriers. 2015 ; Vol. 3, No. 3. pp. 1-35
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AB - 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.

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