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Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147.

Title: Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147.
Authors: Schreiner A; Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, D-60323 Frankfurt am Main, Germany.; Ruonala M; Jakob V; Suthaus J; Boles E; Wouters F; Starzinski-Powitz A
Source: Molecular biology of the cell [Mol Biol Cell] 2007 Apr; Vol. 18 (4), pp. 1272-81. Date of Electronic Publication: 2007 Jan 31.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: American Society for Cell Biology Country of Publication: United States NLM ID: 9201390 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1059-1524 (Print) Linking ISSN: 10591524 NLM ISO Abbreviation: Mol Biol Cell Subsets: MEDLINE
Imprint Name(s): Original Publication: Bethesda, MD : American Society for Cell Biology, c1992-
MeSH Terms: Cell Movement*; Basigin/*metabolism ; Membrane Proteins/*metabolism; Basigin/genetics ; Endometriosis/pathology ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Membrane Proteins/genetics ; Microscopy, Fluorescence/methods ; Peptide Fragments/metabolism ; Ubiquitin/metabolism ; Yeasts/genetics ; Yeasts/metabolism ; Animals ; Base Sequence ; Cell Adhesion Molecules ; Cells, Cultured ; Dogs ; Female ; Humans ; Immunoprecipitation ; Molecular Sequence Data ; Neoplasm Invasiveness ; RNA, Small Interfering
Abstract: 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.
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Substance Nomenclature: 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 (Basigin); EC 3.4.24.24 (Col-1 peptide, human); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (Matrix Metalloproteinase 9)
Entry Date(s): Date Created: 20070203 Date Completed: 20070604 Latest Revision: 20181113
Update Code: 20260130
PubMed Central ID: PMC1838978
DOI: 10.1091/mbc.e06-07-0637
PMID: 17267690
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't