Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition
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 PGE2 enhances the nuclear funct...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 17, 2016
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| In: |
OncoTarget
Year: 2016, Jahrgang: 7, Heft: 29, Pages: 46354-46370 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.10128 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.18632/oncotarget.10128 Verlag, kostenfrei, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10128&path[]=31870 
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| Verfasserangaben: | Sepp R. Jansen, Wilfred J. Poppinga, Wim de Jager, Frank Lezoualc'h, Xiaodong Cheng, Thomas Wieland, Stephen J. Yarwood, Reinoud Gosens, Martina Schmidt |
| Zusammenfassung: | 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 PGE2 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 PGE2 in non-small cell lung carcinoma cells. We show that PGE2 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 PGE2 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 PGE2-induced EMT and subsequent activation of β-catenin. |
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| Beschreibung: | Gesehen am 08.07.2019 Im Titel ist die Zahl "2" tiefgestellt |
| Beschreibung: | Online Resource |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.10128 |