| Loss of desmocollin-2 confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/β-catenin signaling. | |
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MedLine Citation:
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PMID: 21325624 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Desmocollin-2 (Dsc2) and desmoglein-2 (Dsg2) are transmembrane cell adhesion proteins of desmosomes. Reduced expression of Dsc2 has been reported in colorectal carcinomas, suggesting that Dsc2 may play a role in the development and/or progression of colorectal cancer. However, no studies have examined the mechanistic contribution of Dsc2 deficiency to tumorigenesis. Here we report that loss of Dsc2 promotes cell proliferation and enables tumor growth in vivo through the activation of Akt/β-catenin signaling. Inhibition of Akt prevented the increase in β-catenin-dependent transcription and proliferation following Dsc2 knockdown and attenuated the in vivo growth of Dsc2-deficient cells. Taken together, our results provide evidence that loss of Dsc2 contributes to the growth of colorectal cancer cells and highlight a novel mechanism by which the desmosomal cadherins regulate β-catenin signaling. |
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Authors:
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Keli Kolegraff; Porfirio Nava; My N Helms; Charles A Parkos; Asma Nusrat |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-16 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 22 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-18 Completed Date: 2011-08-16 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1121-34 Citation Subset: IM |
Affiliation:
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Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Caco-2 Cells Cell Proliferation Colon / metabolism, pathology Colonic Neoplasms / genetics, metabolism*, pathology Colorectal Neoplasms / genetics, metabolism*, pathology Desmocollins* / deficiency, genetics Desmoglein 2 / genetics, metabolism Desmosomes / genetics, metabolism, pathology Gene Expression Regulation, Neoplastic Gene Silencing Humans Mice Mice, Knockout Oncogene Protein v-akt / antagonists & inhibitors, genetics, metabolism* Phenotype Protein Kinase Inhibitors / pharmacology RNA, Small Interfering / metabolism Signal Transduction / drug effects, genetics Transcription, Genetic Transfection beta Catenin / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK-55679/DK/NIDDK NIH HHS; DK-59888/DK/NIDDK NIH HHS; DK-61739/DK/NIDDK NIH HHS; R01 DK059888/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DSC2 protein, human; 0/Desmocollins; 0/Desmoglein 2; 0/Protein Kinase Inhibitors; 0/RNA, Small Interfering; 0/beta Catenin; EC 2.7.11.1/Oncogene Protein v-akt |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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