Document Detail

Numb is a negative regulator of HGF dependent cell scattering and Rac1 activation.
MedLine Citation:
PMID:  21147098     Owner:  NLM     Status:  In-Data-Review    
Numb is an endocytic adaptor protein that regulates internalization and post-endocytic trafficking of cell surface proteins. In polarized epithelial cells Numb is localized to the basolateral membrane, and recent work has implicated Numb in regulation of cell adhesion and migration, suggesting a role for Numb in epithelial-mesenchymal transition (EMT). We depleted MDCK cells of Numb and examined the effects downstream of EMT-promoting stimuli. While knockdown of Numb did not affect apicobasal polarity, we show that depletion of Numb destabilizes E-cadherin-based cell-cell adhesion and promotes loss of epithelial cell morphology. In addition, Numb knockdown in MDCK cells potentiates HGF-induced lamellipodia formation and cell dispersal. Examination of Rac1-GTP levels in Numb knockdown cells revealed hyperactivation of Rac1 following extracellular calcium depletion and HGF stimulation, which corresponds with enhanced loss of cell adhesions and lamellipodia formation. Furthermore, inhibition of Rac1 in Numb depleted cells stabilized cell-cell contacts following depletion of extracellular calcium. Together, these data indicate that Numb acts to suppress Rac1-GTP accumulation, and its loss leads to increased sensitivity toward extracellular signals that disrupt cell-cell adhesion to induce epithelial-mesenchymal transition (EMT) and cell dispersal.
Kimberly M Lau; C Jane McGlade
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Publication Detail:
Type:  Journal Article     Date:  2010-12-11
Journal Detail:
Title:  Experimental cell research     Volume:  317     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  539-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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