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Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene
CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC) cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428361/ https://www.ncbi.nlm.nih.gov/pubmed/22952674 http://dx.doi.org/10.1371/journal.pone.0043399 |
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author | Zhao, Tiansuo Gao, Song Wang, Xiuchao Liu, Jingcheng Duan, Yitao Yuan, Zhanna Sheng, Jun Li, Shasha Wang, Feng Yu, Ming Ren, He Hao, Jihui |
author_facet | Zhao, Tiansuo Gao, Song Wang, Xiuchao Liu, Jingcheng Duan, Yitao Yuan, Zhanna Sheng, Jun Li, Shasha Wang, Feng Yu, Ming Ren, He Hao, Jihui |
author_sort | Zhao, Tiansuo |
collection | PubMed |
description | CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC) cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF)-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α bound to the hypoxia-response element (HRE; 5′-A/GCGTG-3′) of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC. |
format | Online Article Text |
id | pubmed-3428361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34283612012-09-05 Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene Zhao, Tiansuo Gao, Song Wang, Xiuchao Liu, Jingcheng Duan, Yitao Yuan, Zhanna Sheng, Jun Li, Shasha Wang, Feng Yu, Ming Ren, He Hao, Jihui PLoS One Research Article CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC) cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF)-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α bound to the hypoxia-response element (HRE; 5′-A/GCGTG-3′) of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC. Public Library of Science 2012-08-27 /pmc/articles/PMC3428361/ /pubmed/22952674 http://dx.doi.org/10.1371/journal.pone.0043399 Text en © 2012 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhao, Tiansuo Gao, Song Wang, Xiuchao Liu, Jingcheng Duan, Yitao Yuan, Zhanna Sheng, Jun Li, Shasha Wang, Feng Yu, Ming Ren, He Hao, Jihui Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title | Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title_full | Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title_fullStr | Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title_full_unstemmed | Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title_short | Hypoxia-Inducible Factor-1α Regulates Chemotactic Migration of Pancreatic Ductal Adenocarcinoma Cells through Directly Transactivating the CX3CR1 Gene |
title_sort | hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the cx3cr1 gene |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428361/ https://www.ncbi.nlm.nih.gov/pubmed/22952674 http://dx.doi.org/10.1371/journal.pone.0043399 |
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