Thodeti Charles Kumar, Fröhlich Camilla, Nielsen Christian Kamp, Takada Yoshikazu, Fässler Reinhard, Albrechtsen Reidar, Wewer Ulla M
Institute of Molecular Pathology, University of Copenhagen, Frederik Vs vej 11, Denmark.
FEBS Lett. 2005 Oct 24;579(25):5589-95. doi: 10.1016/j.febslet.2005.09.024. Epub 2005 Sep 28.
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.
去整合素和金属蛋白酶12（ADAM12）已被证明在人类恶性肿瘤中上调，并在乳腺癌小鼠模型中加速恶性表型。ADAM12是β1整合素的底物，可能通过与β1整合素结合影响肿瘤和基质细胞行为。在此，我们报告β1整合素缺陷或β3整合素过表达的细胞可通过β3整合素与重组全长人ADAM12结合。此外，细胞通过β3整合素与ADAM12结合导致粘着斑形成，而β1整合素介导的细胞附着则不会形成粘着斑。我们还表明，RhoA参与β3整合素介导的粘着斑形成。
