<it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled
<p>Abstract</p> <p>Background</p> <p>The human microbial pathogen <it>Helicobacter pylori </it>resides in the stomach of about fifty percent of the world's population and represents a risk factor for chronic gastritis, peptic ulcers and, in rare cases,...
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| Format: | Article |
| Language: | English |
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BMC
2010-02-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/9/1/31 |
| _version_ | 1811278978412969984 |
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| author | Lendeckel Uwe Leverkus Martin Feoktistova Maria Gnad Thorsten Naumann Michael |
| author_facet | Lendeckel Uwe Leverkus Martin Feoktistova Maria Gnad Thorsten Naumann Michael |
| author_sort | Lendeckel Uwe |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The human microbial pathogen <it>Helicobacter pylori </it>resides in the stomach of about fifty percent of the world's population and represents a risk factor for chronic gastritis, peptic ulcers and, in rare cases, gastric cancer. Alterations of the Wnt/β-catenin signaling pathway have been described in almost every human cancer disease, due to the regulation of target genes being involved in cell cycle control, differentiation, cell migration or stem cell control. Our study aimed to elucidate the role of proximal Wnt signaling components low density lipoprotein receptor-related protein 6 (LRP6) and Dishevelled (Dvl) in the activation of β-catenin early after infection of gastric epithelial cells with <it>H. pylori</it>.</p> <p>Results</p> <p>Infection of gastric epithelial NCI-N87 cells with <it>H. pylori </it>induces rapid phosphorylation of the Wnt/β-catenin pathway co-receptor LRP6 independent of the cytotoxin-associated gene A (CagA) or vacuolating cytotoxin A (VacA). However, bacteria lacking a functional type 4 secretion system (T4SS) failed to induce LRP6 phosphorylation. Further, we identified proteins of the Dvl family, namely Dvl2 and Dvl3, which are involved in LRP6 phosphorylation. <it>H. pylori</it>-induced nuclear accumulation of β-catenin and its transcriptional activation, and expression of Wnt target genes are strongly reduced in stable knockdown cell lines deficient for LRP6, Dvl2 or Dvl3.</p> <p>Conclusion</p> <p>We analysed the <it>H. pylori</it>-induced activation of Wnt-signaling factors and demonstrate for the first time that the canonical Wnt-signaling proteins LRP6 and Dvl2 and Dvl3 are involved in the regulation of β-catenin.</p> |
| first_indexed | 2024-04-13T00:45:24Z |
| format | Article |
| id | doaj.art-7bb9f43b81f947199774096decf1122f |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-13T00:45:24Z |
| publishDate | 2010-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-7bb9f43b81f947199774096decf1122f2022-12-22T03:10:01ZengBMCMolecular Cancer1476-45982010-02-01913110.1186/1476-4598-9-31<it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and DishevelledLendeckel UweLeverkus MartinFeoktistova MariaGnad ThorstenNaumann Michael<p>Abstract</p> <p>Background</p> <p>The human microbial pathogen <it>Helicobacter pylori </it>resides in the stomach of about fifty percent of the world's population and represents a risk factor for chronic gastritis, peptic ulcers and, in rare cases, gastric cancer. Alterations of the Wnt/β-catenin signaling pathway have been described in almost every human cancer disease, due to the regulation of target genes being involved in cell cycle control, differentiation, cell migration or stem cell control. Our study aimed to elucidate the role of proximal Wnt signaling components low density lipoprotein receptor-related protein 6 (LRP6) and Dishevelled (Dvl) in the activation of β-catenin early after infection of gastric epithelial cells with <it>H. pylori</it>.</p> <p>Results</p> <p>Infection of gastric epithelial NCI-N87 cells with <it>H. pylori </it>induces rapid phosphorylation of the Wnt/β-catenin pathway co-receptor LRP6 independent of the cytotoxin-associated gene A (CagA) or vacuolating cytotoxin A (VacA). However, bacteria lacking a functional type 4 secretion system (T4SS) failed to induce LRP6 phosphorylation. Further, we identified proteins of the Dvl family, namely Dvl2 and Dvl3, which are involved in LRP6 phosphorylation. <it>H. pylori</it>-induced nuclear accumulation of β-catenin and its transcriptional activation, and expression of Wnt target genes are strongly reduced in stable knockdown cell lines deficient for LRP6, Dvl2 or Dvl3.</p> <p>Conclusion</p> <p>We analysed the <it>H. pylori</it>-induced activation of Wnt-signaling factors and demonstrate for the first time that the canonical Wnt-signaling proteins LRP6 and Dvl2 and Dvl3 are involved in the regulation of β-catenin.</p>http://www.molecular-cancer.com/content/9/1/31 |
| spellingShingle | Lendeckel Uwe Leverkus Martin Feoktistova Maria Gnad Thorsten Naumann Michael <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled Molecular Cancer |
| title | <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled |
| title_full | <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled |
| title_fullStr | <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled |
| title_full_unstemmed | <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled |
| title_short | <it>Helicobacter pylori</it>-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled |
| title_sort | it helicobacter pylori it induced activation of β catenin involves low density lipoprotein receptor related protein 6 and dishevelled |
| url | http://www.molecular-cancer.com/content/9/1/31 |
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