title: ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins.
abstract: ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to beta1 integrins. Here, we report that cells deficient in beta1 integrin or overexpressing beta3 integrin can bind to recombinant full-length human ADAM12 via beta3 integrin. Furthermore, cell binding to ADAM12 via beta3 integrin results in the formation of focal adhesions, which are not formed upon beta1 integrin-mediated cell attachment. We also show that RhoA is involved in beta3 integrin-mediated focal adhesion formation.
authors.affiliation: Institute of Molecular Pathology, University of Copenhagen, Frederik Vs vej 11, Denmark.
authors.forename: Charles Kumar
authors.initials: CK
authors.lastname: Thodeti
authors.forename: Camilla
authors.initials: C
authors.lastname: Fröhlich
authors.forename: Christian Kamp
authors.initials: CK
authors.lastname: Nielsen
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takada
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Reidar
authors.initials: R
authors.lastname: Albrechtsen
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Wewer
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072199:ADAM12 Protein; D045744:Cell Line, Tumor; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011994:Recombinant Proteins; C094990:adhesion receptor; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D020742:rhoA GTP-Binding Protein