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Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection
The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines the availability of β-catenin. Another common feature of solid tumors is the presence of hypoxia as i...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965681/ https://www.ncbi.nlm.nih.gov/pubmed/20844082 http://dx.doi.org/10.1091/mbc.E10-04-0312 |
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author | Newton, Ian P. Kenneth, Niall S. Appleton, Paul L. Näthke, Inke Rocha, Sonia |
author_facet | Newton, Ian P. Kenneth, Niall S. Appleton, Paul L. Näthke, Inke Rocha, Sonia |
author_sort | Newton, Ian P. |
collection | PubMed |
description | The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines the availability of β-catenin. Another common feature of solid tumors is the presence of hypoxia as indicated by the up-regulation of hypoxia-inducible factors (HIFs) such as HIF-1α. Here, we demonstrate a novel link between APC and hypoxia and show that APC and HIF-1α antagonize each other. Hypoxia results in reduced levels of APC mRNA and protein via a HIF-1α–dependent mechanism. HIF-1α represses the APC gene via a functional hypoxia-responsive element on the APC promoter. In contrast, APC-mediated repression of HIF-1α requires wild-type APC, low levels of β-catenin, and nuclear factor-κB activity. These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions. |
format | Text |
id | pubmed-2965681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29656812011-01-16 Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection Newton, Ian P. Kenneth, Niall S. Appleton, Paul L. Näthke, Inke Rocha, Sonia Mol Biol Cell Articles The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines the availability of β-catenin. Another common feature of solid tumors is the presence of hypoxia as indicated by the up-regulation of hypoxia-inducible factors (HIFs) such as HIF-1α. Here, we demonstrate a novel link between APC and hypoxia and show that APC and HIF-1α antagonize each other. Hypoxia results in reduced levels of APC mRNA and protein via a HIF-1α–dependent mechanism. HIF-1α represses the APC gene via a functional hypoxia-responsive element on the APC promoter. In contrast, APC-mediated repression of HIF-1α requires wild-type APC, low levels of β-catenin, and nuclear factor-κB activity. These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions. The American Society for Cell Biology 2010-11-01 /pmc/articles/PMC2965681/ /pubmed/20844082 http://dx.doi.org/10.1091/mbc.E10-04-0312 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). |
spellingShingle | Articles Newton, Ian P. Kenneth, Niall S. Appleton, Paul L. Näthke, Inke Rocha, Sonia Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title | Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title_full | Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title_fullStr | Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title_full_unstemmed | Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title_short | Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1α Have an Antagonistic Connection |
title_sort | adenomatous polyposis coli and hypoxia-inducible factor-1α have an antagonistic connection |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965681/ https://www.ncbi.nlm.nih.gov/pubmed/20844082 http://dx.doi.org/10.1091/mbc.E10-04-0312 |
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