Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147.
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.
Schreiner
Alexander
A
Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, D-60323 Frankfurt am Main, Germany.
Ruonala
Mika
M
Jakob
Viktor
V
Suthaus
Jan
J
Boles
Eckhard
E
Wouters
Fred
F
Starzinski-Powitz
Anna
A
D000818:Animals; D001483:Base Sequence; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D004715:Endometriosis / Q000473:pathology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000378:metabolism; D034741:RNA, Small Interfering; D025801:Ubiquitin / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
C483313:AJAP1 protein, human; C497886:BSG protein, human; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D025801:Ubiquitin; D051926:Basigin; C471083:Col-1 peptide, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9