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• W2444596056 abstract "// Sepp R. Jansen 1, 4 , Wilfred J. Poppinga 1 , Wim de Jager 1 , Frank Lezoualc’h 2 , Xiaodong Cheng 3 , Thomas Wieland 4 , Stephen J. Yarwood 5 , Reinoud Gosens 1 , Martina Schmidt 1 1 Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy (GRIP), University of Groningen, Groningen, The Netherlands 2 Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Université Toulouse III, Toulouse, France 3 Department of Integrative Biology & Pharmacology, Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas, Houston, TX, USA 4 Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany 5 School of Life Sciences, Heriot-Watt University, Edinburgh, Scotland Correspondence to: Sepp R. Jansen, email: sepp.jansen@medma.uni-heidelberg.de Keywords: PGE 2 , Epac, β-catenin, Ezrin, EMT Received: January 12, 2016     Accepted: June 02, 2016     Published: June 17, 2016 ABSTRACT In epithelial cells, β-catenin is localized at cell-cell junctions where it stabilizes adherens junctions. When these junctions are disrupted, β-catenin can translocate to the nucleus where it functions as a transcriptional cofactor. Recent research has indicated that PGE 2 enhances the nuclear function of β-catenin through cyclic AMP. Here, we aim to study the role of the cyclic AMP effector Epac in β-catenin activation by PGE 2 in non-small cell lung carcinoma cells. We show that PGE 2 induces a down-regulation of E-cadherin, promotes cell migration and enhances β-catenin translocation to the nucleus. This results in β-catenin-dependent gene transcription. We also observed increased expression of Epac1. Inhibition of Epac1 activity using the CE3F4 compound or Epac1 siRNA abolished the effects of PGE 2 on β-catenin. Further, we observed that Epac1 and β-catenin associate together. Expression of an Epac1 mutant with a deletion in the nuclear pore localization sequence prevents this association. Furthermore, the scaffold protein Ezrin was shown to be required to link Epac1 to β-catenin. This study indicates a novel role for Epac1 in PGE 2 -induced EMT and subsequent activation of β-catenin." @default.
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• W2444596056 date "2016-06-17" @default.
• W2444596056 modified "2023-10-05" @default.
• W2444596056 title "Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition" @default.
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• W2444596056 doi "https://doi.org/10.18632/oncotarget.10128" @default.
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