Hippo pathway elements Co-localize with Occludin: A possible sensor system in pancreatic epithelial cells

摘要: External adherens junction-based cell-cell contacts involving E-cadherin interactions function to sense planar cell status and modulate epithelial proliferation through Hippo (Hpo) non-canonical Wnt pathways signaling. We hypothesized these regulatory processes should also be sensitive a similar contact sensor associated with apical-basal polarity events at surfaces. used 2 human pancreatic cancer lines explore this hypothesis: one the capacity form functional tight junction structures polarize (HPAFII) lacking (AsPc1). Occludin (Ocln), tetraspanning protein TJ capable of establishing external contacts, was observed partially co-localize Hpo elements YAP (c-yes protein) TEAD (TEA-dependent), which drive proliferative transcription program. Treatment dobutamine, known affect YAP, shown suppress in an Ocln-dependent manner. Blockade kinase C-zeta (PKC-ζ) diminished transepithelial electrical resistance (TER) HPAFII monolayers that not corrected by dobutamine treatment while loss TER resulting from inhibition ROCK1 could recovered. Examination normal cancerous biopsies showed cellular localization Ocln, c-Yes, were for cells AsPc1 cells. Together, results suggest link between signals emanating Ocln may regulate coordination events.