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Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway

Prostaglandin E(2) (PGE(2)) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased β1-integrin expression and cell migration; however, the mechanism remains unclear. PGE(2) exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1–4). The present...

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Autores principales: Bai, Xiaoming, Wang, Jie, Guo, Yan, Pan, Jinshun, Yang, Qinyi, Zhang, Min, Li, Hai, Zhang, Li, Ma, Juan, Shi, Feng, Shu, Wei, Wang, Yipin, Leng, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377465/
https://www.ncbi.nlm.nih.gov/pubmed/25289898
http://dx.doi.org/10.1038/srep06538
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author Bai, Xiaoming
Wang, Jie
Guo, Yan
Pan, Jinshun
Yang, Qinyi
Zhang, Min
Li, Hai
Zhang, Li
Ma, Juan
Shi, Feng
Shu, Wei
Wang, Yipin
Leng, Jing
author_facet Bai, Xiaoming
Wang, Jie
Guo, Yan
Pan, Jinshun
Yang, Qinyi
Zhang, Min
Li, Hai
Zhang, Li
Ma, Juan
Shi, Feng
Shu, Wei
Wang, Yipin
Leng, Jing
author_sort Bai, Xiaoming
collection PubMed
description Prostaglandin E(2) (PGE(2)) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased β1-integrin expression and cell migration; however, the mechanism remains unclear. PGE(2) exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1–4). The present study investigated the effect of EP1 receptor activation on β1-integrin expression and cell migration in HCC. Cell migration increased by 60% in cells treated with 17-PT-PGE(2) (EP1 agonist), which was suppressed by pretreatment with a β1-integrin polyclonal antibody. PGE(2) increased β1-integrin expression by approximately 2-fold. EP1 receptor transfection or treatment with 17-PT-PGE(2) mimicked the effect of PGE(2) treatment. EP1 siRNA blocked PGE(2)-mediated β1-integrin expression. 17-PT-PGE(2) treatment induced PKC and NF-κB activation; PKC and NF-κB inhibitors suppressed 17-PT-PGE(2)-mediated β1-integrin expression. FoxC2, a β1-integrin transcription factor, was also upregulated by 17-PT-PGE(2). NF-κB inhibitor suppressed 17-PT-PGE(2)-mediated FoxC2 upregulation. Immunohistochemistry showed p65, FoxC2, EP1 receptor and β1-integrin were all highly expressed in the HCC cases. This study suggested that PGE(2) upregulates β1-integrin expression and cell migration in HCC cells by activating the PKC/NF-κB signaling pathway. Targeting PGE(2)/EP1/PKC/NF-κB/FoxC2/β1-integrin pathway may represent a new therapeutic strategy for the prevention and treatment of this cancer.
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spelling pubmed-53774652017-04-05 Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway Bai, Xiaoming Wang, Jie Guo, Yan Pan, Jinshun Yang, Qinyi Zhang, Min Li, Hai Zhang, Li Ma, Juan Shi, Feng Shu, Wei Wang, Yipin Leng, Jing Sci Rep Article Prostaglandin E(2) (PGE(2)) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased β1-integrin expression and cell migration; however, the mechanism remains unclear. PGE(2) exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1–4). The present study investigated the effect of EP1 receptor activation on β1-integrin expression and cell migration in HCC. Cell migration increased by 60% in cells treated with 17-PT-PGE(2) (EP1 agonist), which was suppressed by pretreatment with a β1-integrin polyclonal antibody. PGE(2) increased β1-integrin expression by approximately 2-fold. EP1 receptor transfection or treatment with 17-PT-PGE(2) mimicked the effect of PGE(2) treatment. EP1 siRNA blocked PGE(2)-mediated β1-integrin expression. 17-PT-PGE(2) treatment induced PKC and NF-κB activation; PKC and NF-κB inhibitors suppressed 17-PT-PGE(2)-mediated β1-integrin expression. FoxC2, a β1-integrin transcription factor, was also upregulated by 17-PT-PGE(2). NF-κB inhibitor suppressed 17-PT-PGE(2)-mediated FoxC2 upregulation. Immunohistochemistry showed p65, FoxC2, EP1 receptor and β1-integrin were all highly expressed in the HCC cases. This study suggested that PGE(2) upregulates β1-integrin expression and cell migration in HCC cells by activating the PKC/NF-κB signaling pathway. Targeting PGE(2)/EP1/PKC/NF-κB/FoxC2/β1-integrin pathway may represent a new therapeutic strategy for the prevention and treatment of this cancer. Nature Publishing Group 2014-10-07 /pmc/articles/PMC5377465/ /pubmed/25289898 http://dx.doi.org/10.1038/srep06538 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Bai, Xiaoming
Wang, Jie
Guo, Yan
Pan, Jinshun
Yang, Qinyi
Zhang, Min
Li, Hai
Zhang, Li
Ma, Juan
Shi, Feng
Shu, Wei
Wang, Yipin
Leng, Jing
Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title_full Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title_fullStr Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title_full_unstemmed Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title_short Prostaglandin E(2) stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway
title_sort prostaglandin e(2) stimulates β1-integrin expression in hepatocellular carcinoma through the ep1 receptor/pkc/nf-κb pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377465/
https://www.ncbi.nlm.nih.gov/pubmed/25289898
http://dx.doi.org/10.1038/srep06538
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