Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition.
Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition.
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DOI：
10.18632/oncotarget.10128
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Schmidt M
中科院分区：
文献类型：
--
作者：
Jansen SR;Poppinga WJ;de Jager W;Lezoualc'h F;Cheng X;Wieland T;Yarwood SJ;Gosens R;Schmidt M
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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影响因子：
37.3
作者：
Brudvik KW;Paulsen JE;Aandahl EM;Roald B;Taskén K
通讯作者：
Taskén K
影响因子：
--
作者：
Carotenuto M;De Antonellis P;Liguori L;Benvenuto G;Magliulo D;Alonzi A;Turino C;Attanasio C;Damiani V;Bello AM;Vitiello F;Pasquinelli R;Terracciano L;Federico A;Fusco A;Freeman J;Dale TC;Decraene C;Chiappetta G;Piantedosi F;Calabrese C;Zollo M
通讯作者：
Zollo M
影响因子：
4
作者：
Gavert, Nancy;Ben-Shmuel, Amir;Ben-Ze'ev, Avri
通讯作者：
Ben-Ze'ev, Avri
DOI：
10.1073/pnas.220413597
发表时间：
2000-10-24
影响因子：
11.1
作者：
Fang, XJ;Yu, SX;Mills, GB
通讯作者：
Mills, GB
影响因子：
4.8
作者：
Fujino, H;West, KA;Regan, JW
通讯作者：
Regan, JW