Document Detail


Loss of desmocollin-2 confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/β-catenin signaling.
MedLine Citation:
PMID:  21325624     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Keli Kolegraff; Porfirio Nava; My N Helms; Charles A Parkos; Asma Nusrat
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-16
Journal Detail:
Title:  Molecular biology of the cell     Volume:  22     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-18     Completed Date:  2011-08-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1121-34     Citation Subset:  IM    
Affiliation:
Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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