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The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells
BACKGROUND: Most cases of colorectal cancer are initiated by hyperactivation of the Wnt/β-catenin pathway due to mutations in the APC tumour suppressor, or in β-catenin itself. A recently discovered component of this pathway is Legless, which is essential for Wnt-induced transcription during Drosoph...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478683/ https://www.ncbi.nlm.nih.gov/pubmed/18627596 http://dx.doi.org/10.1186/1471-2407-8-199 |
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author | de la Roche, Marc Worm, Jesper Bienz, Mariann |
author_facet | de la Roche, Marc Worm, Jesper Bienz, Mariann |
author_sort | de la Roche, Marc |
collection | PubMed |
description | BACKGROUND: Most cases of colorectal cancer are initiated by hyperactivation of the Wnt/β-catenin pathway due to mutations in the APC tumour suppressor, or in β-catenin itself. A recently discovered component of this pathway is Legless, which is essential for Wnt-induced transcription during Drosophila development. Limited functional information is available for its two mammalian relatives, BCL9 and B9L/BCL9-2: like Legless, these proteins bind to β-catenin, and RNAi-mediated depletion of B9L/BCL9-2 has revealed that this protein is required for efficient β-catenin-mediated transcription in mammalian cell lines. No loss-of-function data are available for BCL9. METHODS: We have used overexpression of dominant-negative forms of BCL9, and RNAi-mediated depletion, to study its function in human cell lines with elevated Wnt pathway activity, including colorectal cancer cells. RESULTS: We found that BCL9 is required for efficient β-catenin-mediated transcription in Wnt-stimulated HEK 293 cells, and in the SW480 colorectal cancer cell line whose Wnt pathway is active due to APC mutation. Dominant-negative mutants of BCL9 indicated that its function depends not only on its β-catenin ligand, but also on an unknown ligand of its C-terminus. Finally, we show that BCL9 and B9L are both Wnt-inducible genes, hyperexpressed in colorectal cancer cell lines, indicating that they are part of a positive feedback loop. CONCLUSION: BCL9 is required for efficient β-catenin-mediated transcription in human cell lines whose Wnt pathway is active, including colorectal cancer cells, indicating its potential as a drug target in colorectal cancer. |
format | Text |
id | pubmed-2478683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-24786832008-07-22 The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells de la Roche, Marc Worm, Jesper Bienz, Mariann BMC Cancer Research Article BACKGROUND: Most cases of colorectal cancer are initiated by hyperactivation of the Wnt/β-catenin pathway due to mutations in the APC tumour suppressor, or in β-catenin itself. A recently discovered component of this pathway is Legless, which is essential for Wnt-induced transcription during Drosophila development. Limited functional information is available for its two mammalian relatives, BCL9 and B9L/BCL9-2: like Legless, these proteins bind to β-catenin, and RNAi-mediated depletion of B9L/BCL9-2 has revealed that this protein is required for efficient β-catenin-mediated transcription in mammalian cell lines. No loss-of-function data are available for BCL9. METHODS: We have used overexpression of dominant-negative forms of BCL9, and RNAi-mediated depletion, to study its function in human cell lines with elevated Wnt pathway activity, including colorectal cancer cells. RESULTS: We found that BCL9 is required for efficient β-catenin-mediated transcription in Wnt-stimulated HEK 293 cells, and in the SW480 colorectal cancer cell line whose Wnt pathway is active due to APC mutation. Dominant-negative mutants of BCL9 indicated that its function depends not only on its β-catenin ligand, but also on an unknown ligand of its C-terminus. Finally, we show that BCL9 and B9L are both Wnt-inducible genes, hyperexpressed in colorectal cancer cell lines, indicating that they are part of a positive feedback loop. CONCLUSION: BCL9 is required for efficient β-catenin-mediated transcription in human cell lines whose Wnt pathway is active, including colorectal cancer cells, indicating its potential as a drug target in colorectal cancer. BioMed Central 2008-07-15 /pmc/articles/PMC2478683/ /pubmed/18627596 http://dx.doi.org/10.1186/1471-2407-8-199 Text en Copyright © 2008 de la Roche et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article de la Roche, Marc Worm, Jesper Bienz, Mariann The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title | The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title_full | The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title_fullStr | The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title_full_unstemmed | The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title_short | The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells |
title_sort | function of bcl9 in wnt/β-catenin signaling and colorectal cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478683/ https://www.ncbi.nlm.nih.gov/pubmed/18627596 http://dx.doi.org/10.1186/1471-2407-8-199 |
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