Document Detail

Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147.
MedLine Citation:
PMID:  17267690     Owner:  NLM     Status:  MEDLINE    
Shrew-1 was previously isolated from an endometriotic cell line in our search for invasion-associated genes. It proved to be a membrane protein that targets to the basolateral membrane of polarized epithelial cells, interacting with E-cadherin-catenin complexes of adherens junctions. Paradoxically, the existence of adherens junctions is incompatible with invasion. To investigate whether shrew-1 can indeed influence cellular invasion, we overexpressed it in HT1080 fibrosarcoma cells. This resulted in enhanced invasiveness, accompanied by an increased matrix metalloprotease (MMP)-9 level in the supernatant, raising the question about the role of shrew-1 in this process. Logic suggested we looked for an interaction with CD147, a known promoter of invasiveness and MMP activity. Indeed, genetics-based, biochemical, and microscopy experiments revealed shrew-1- and CD147-containing complexes in invasive endometriotic cells and an interaction in epithelial cells, which was stronger in MCF7 tumor cells, but weaker in Madin-Darby canine kidney cells. In contrast to the effect mediated by overexpression, small interfering RNA-mediated down-regulation of either shrew-1 or CD147 in HeLa cells decreased invasiveness without affecting the proliferation behavior of HeLa cells, but the knockdown cells displayed decreased motility. Altogether, our results imply that shrew-1 has a function in the regulation of cellular invasion, which may involve its interaction with CD147.
Alexander Schreiner; Mika Ruonala; Viktor Jakob; Jan Suthaus; Eckhard Boles; Fred Wouters; Anna Starzinski-Powitz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-31
Journal Detail:
Title:  Molecular biology of the cell     Volume:  18     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-29     Completed Date:  2007-06-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1272-81     Citation Subset:  IM    
Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, D-60323 Frankfurt am Main, Germany.
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MeSH Terms
Antigens, CD147 / genetics,  metabolism*
Base Sequence
Cell Adhesion Molecules
Cell Movement*
Cells, Cultured
Endometriosis / pathology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Membrane Proteins / genetics,  metabolism*
Microscopy, Fluorescence / methods
Molecular Sequence Data
Neoplasm Invasiveness
Peptide Fragments / metabolism
RNA, Small Interfering
Ubiquitin / metabolism
Yeasts / genetics,  metabolism
Reg. No./Substance:
0/AJAP1 protein, human; 0/BSG protein, human; 0/Cell Adhesion Molecules; 0/Membrane Proteins; 0/Peptide Fragments; 0/RNA, Small Interfering; 0/Ubiquitin; 136894-56-9/Antigens, CD147; EC peptide, human; EC Metalloproteinase 2; EC Metalloproteinase 9

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