Document Detail

Nm23-H1 regulates contact inhibition of locomotion which is affected by ephrin-B1.
MedLine Citation:
PMID:  22718351     Owner:  NLM     Status:  Publisher    
Contact inhibition of locomotion (CIL) is the process by which cells stop the continual migration in the same direction after collision with another cell. Highly invasive malignant cells exhibit diminished CIL behavior when they contact with stromal cells, which allows stromal invasion of tumors. We show that Nm23-H1 is essential for the suppression of Rac1 through inactivation of Tiam1 at the sites of cell-cell contact, which plays a pivotal role in CIL. U87MG cells show CIL when they contact with normal glia. U87MG did not invade significantly into glias in spheroid confrontation assay, whereas reduction of Nm23-H1 expression in U87MG cells abrogates CIL and they invaded into glias. In U87MG cells, Nm23-H1 is translocated to the sites of contact with glia through association with α-catenin and N-cadherin. In the expression of wild type Nm23-H1, neither Nm23-H1 mutant, which lacks the binding ability with Tiam1, nor α-catenin recovered CIL. Moreover, the expression of ephrin-B1 in tumor cells disrupted CIL and promoted invasion. As one mechanism, ephrin-B1 inhibits the association of Nm23-H1 with Tiam1, which contributes for activation of Rac1. These results indicate a novel function of Nm23-H1 to control CIL, and its negative regulation by ephrin-B1.
Masamitsu Tanaka; Sei Kuriyama; Namiko Aiba
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-20
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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