NDLI: Prostaglandin E$_{2}$ receptor EP1 phosphorylate CREB and mediates MMP2 expression in human cholangiocarcinoma cells

Content Provider	Springer Nature Link
Author	Sun, Bo Rong, Rong Jiang, Hai Zhang, Hai Wang, YiPin Bai, Xiaoming Zhang, Min Ma, Juan Xia, Shukai Shu, Wei Zhang, Li Leng, Jing
Copyright Year	2013
Abstract	Cyclooxygenase-2 (COX-2) and COX-2-induced prostaglandin E$_{2}$ (PGE$_{2}$) have been implicated in all stages of malignant tumorigenesis. Although many aspects of matrix metalloproteinase (MMP2) on tumor invasion have been studied, the exact mechanism of PGE$_{2}$-induced MMP2 overproduction has not been clearly defined. We have previously demonstrated that PGE$_{2}$-enhanced extracellular signal-regulated kinase (Erk) phosphorylation via EP1 signaling pathway involved in PGE$_{2}$-induced cell proliferation. Based on the identification of the transcription factor cyclic AMP response element-binding protein (CREB) as an important regulator of MMP2 and Erk phosphorylate CREB at ser133, we hypothesize that CREB may be implicated in the signaling of PGE$_{2}$ stimulation to MMP2 overproduction via EP1 receptor. In the study, we investigated the role of EP1 receptor on PGE$_{2}$-induced MMP2 expression and delineated the signaling pathway that contributes to EP1 receptor modulation of MMP2 in human cholangiocarcinoma cells. We found PGE$_{2}$ or selective EP1 receptor agonist 17-P-T-PGE$_{2}$-stimulated MMP2 expression and selective EP1 receptor antagonist SC-51322 or EP1 receptor siRNA abrogated PGE$_{2}$-induced MMP2 expression. Intracellular calcium chelator BAPTA-AM, the selective inhibitor of EGFR AG1478 and the selective inhibitor of Erk PD98059 blocked EP1 receptor activation-induced CREB phosphorylation and MMP2 expression. A novel dominant-negative (D-N) inhibitor protein of the CREB, termed A-CREB, attenuated EP1 receptor activation-induced MMP2 expression. Our findings suggest that PGE2-enhanced MMP2 expression is, at least in part, mediated through EP1 receptors and calcium signaling pathway-induced CREB phosphorylation in human cholangiocarcinoma cells.
Starting Page	195
Ending Page	203
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	378
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2013-03-15
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cholangiocarcinoma PGE$_{2}$ EP1 receptor CREB MMP2 Biochemistry Medical Biochemistry Oncology Cardiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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