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AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer

The basic helix-loop-helix transcription factor AP4/TFAP4/AP-4 is encoded by a c-MYC target gene and displays up-regulation concomitantly with c-MYC in colorectal cancer (CRC) and numerous other tumor types. Here a genome-wide characterization of AP4 DNA binding and mRNA expression was performed usi...

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Autores principales: Jackstadt, Rene, Röh, Simone, Neumann, Jens, Jung, Peter, Hoffmann, Reinhard, Horst, David, Berens, Christian, Bornkamm, Georg W., Kirchner, Thomas, Menssen, Antje, Hermeking, Heiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698521/
https://www.ncbi.nlm.nih.gov/pubmed/23752226
http://dx.doi.org/10.1084/jem.20120812
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author Jackstadt, Rene
Röh, Simone
Neumann, Jens
Jung, Peter
Hoffmann, Reinhard
Horst, David
Berens, Christian
Bornkamm, Georg W.
Kirchner, Thomas
Menssen, Antje
Hermeking, Heiko
author_facet Jackstadt, Rene
Röh, Simone
Neumann, Jens
Jung, Peter
Hoffmann, Reinhard
Horst, David
Berens, Christian
Bornkamm, Georg W.
Kirchner, Thomas
Menssen, Antje
Hermeking, Heiko
author_sort Jackstadt, Rene
collection PubMed
description The basic helix-loop-helix transcription factor AP4/TFAP4/AP-4 is encoded by a c-MYC target gene and displays up-regulation concomitantly with c-MYC in colorectal cancer (CRC) and numerous other tumor types. Here a genome-wide characterization of AP4 DNA binding and mRNA expression was performed using a combination of microarray, genome-wide chromatin immunoprecipitation, next-generation sequencing, and bioinformatic analyses. Thereby, hundreds of induced and repressed AP4 target genes were identified. Besides many genes involved in the control of proliferation, the AP4 target genes included markers of stemness (LGR5 and CD44) and epithelial–mesenchymal transition (EMT) such as SNAIL, E-cadherin/CDH1, OCLN, VIM, FN1, and the Claudins 1, 4, and 7. Accordingly, activation of AP4 induced EMT and enhanced migration and invasion of CRC cells. Conversely, down-regulation of AP4 resulted in mesenchymal–epithelial transition and inhibited migration and invasion. In addition, AP4 induction was required for EMT, migration, and invasion caused by ectopic expression of c-MYC. Inhibition of AP4 in CRC cells resulted in decreased lung metastasis in mice. Elevated AP4 expression in primary CRC significantly correlated with liver metastasis and poor patient survival. These findings imply AP4 as a new regulator of EMT that contributes to metastatic processes in CRC and presumably other carcinomas.
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spelling pubmed-36985212014-01-01 AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer Jackstadt, Rene Röh, Simone Neumann, Jens Jung, Peter Hoffmann, Reinhard Horst, David Berens, Christian Bornkamm, Georg W. Kirchner, Thomas Menssen, Antje Hermeking, Heiko J Exp Med Article The basic helix-loop-helix transcription factor AP4/TFAP4/AP-4 is encoded by a c-MYC target gene and displays up-regulation concomitantly with c-MYC in colorectal cancer (CRC) and numerous other tumor types. Here a genome-wide characterization of AP4 DNA binding and mRNA expression was performed using a combination of microarray, genome-wide chromatin immunoprecipitation, next-generation sequencing, and bioinformatic analyses. Thereby, hundreds of induced and repressed AP4 target genes were identified. Besides many genes involved in the control of proliferation, the AP4 target genes included markers of stemness (LGR5 and CD44) and epithelial–mesenchymal transition (EMT) such as SNAIL, E-cadherin/CDH1, OCLN, VIM, FN1, and the Claudins 1, 4, and 7. Accordingly, activation of AP4 induced EMT and enhanced migration and invasion of CRC cells. Conversely, down-regulation of AP4 resulted in mesenchymal–epithelial transition and inhibited migration and invasion. In addition, AP4 induction was required for EMT, migration, and invasion caused by ectopic expression of c-MYC. Inhibition of AP4 in CRC cells resulted in decreased lung metastasis in mice. Elevated AP4 expression in primary CRC significantly correlated with liver metastasis and poor patient survival. These findings imply AP4 as a new regulator of EMT that contributes to metastatic processes in CRC and presumably other carcinomas. The Rockefeller University Press 2013-07-01 /pmc/articles/PMC3698521/ /pubmed/23752226 http://dx.doi.org/10.1084/jem.20120812 Text en © 2013 Jackstadt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Jackstadt, Rene
Röh, Simone
Neumann, Jens
Jung, Peter
Hoffmann, Reinhard
Horst, David
Berens, Christian
Bornkamm, Georg W.
Kirchner, Thomas
Menssen, Antje
Hermeking, Heiko
AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title_full AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title_fullStr AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title_full_unstemmed AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title_short AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
title_sort ap4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698521/
https://www.ncbi.nlm.nih.gov/pubmed/23752226
http://dx.doi.org/10.1084/jem.20120812
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