Document Detail


The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes.
MedLine Citation:
PMID:  18246119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In epithelial cells, the tight junction divides the plasma membrane into distinct apical and basolateral domains. Polarization is essential for epithelial cell function, and apico-basal cell polarity is lost during the epithelial to mesenchymal transition (EMT), a program of events characterized not only by loss of cell polarity, but also by enhanced cell motility and increased cell invasion. Among several apically localized protein complexes, the Crumbs and Par protein complexes have pivotal roles in control of epithelial polarity and apical membrane formation. Here, we demonstrate that the Snail transcriptional repressor antagonizes expression of the Crumbs polarity complex. We show that Snail abolishes localization of the Crumbs and Par complexes to the tight junction, decreases Crumbs complex protein levels and suppresses Crumbs3 transcription. Evidence that Snail acts directly to antagonize Crumbs3 promoter activity is presented. Strikingly, we note that reexpression of exogenous Crumbs3 in Snail-expressing Madin-Darby Canine Kidney cells partially restores cell-cell junctions. Moreover, we find that the EMT inducer transforming growth factor-beta elicits transcriptional repression of Crumbs3 and results in a measurable loss of Crumbs3 protein. Our findings provide new insights into the links between the transcriptional repression function of Snail and its role in antagonizing key apico-basal polarity factors during EMT.
Authors:
E L Whiteman; C-J Liu; E R Fearon; B Margolis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-02-04
Journal Detail:
Title:  Oncogene     Volume:  27     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-19     Completed Date:  2008-08-12     Revised Date:  2010-12-03    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3875-9     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Membrane / physiology
Cell Movement / physiology
Cell Polarity / genetics
Dogs
Epithelial Cells / cytology,  physiology
Gene Expression Regulation, Neoplastic
Kidney
Membrane Glycoproteins / genetics*
Mesoderm / cytology,  physiology
Tight Junctions / genetics,  physiology
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
5-F32-GM07996/GM/NIGMS NIH HHS; 5-P60-DK20572/DK/NIDDK NIH HHS; 5-T32-CA09676/CA/NCI NIH HHS; DK058208/DK/NIDDK NIH HHS; DK069605/DK/NIDDK NIH HHS; R01 DK058208-06/DK/NIDDK NIH HHS; R01 DK069605-04/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CRB3 protein, human; 0/Membrane Glycoproteins; 0/Transcription Factors; 0/snail family transcription factors
Comments/Corrections

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