title: Down-regulation of cell adhesion via rho-associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin-511.
abstract: Epithelial cells, both normal and precancerous, stably anchor to basement membranes, whereas malignant tumors pass through them to achieve metastasis. Of basement membrane components, laminin-511 (α5, β1, γ1; LM-511) has been found to be a major isoform in many adult basement membranes. Several studies have shown that LM-511 promotes not only cell adhesion but also tumor cell migration. Thus, LM-511 can be viewed like two distinct molecules in normal vs. tumor cells; tumor cells seem to be able to alter their response (adhesive vs. migratory) to LM-511. In this study we examined the effects of biologically active molecules on A549 lung adenocarcinoma cell adhesion to LM-511. Of them, phorbol 12-myristate 13-acetate (PMA) induced transition to a rounded cell shape and significantly promoted cell migration on LM-511. The attachment of PMA-treated A549 cells to LM-511 was weaker than that of control cells. PMA-stimulated signaling pathway reduced the binding of integrin α3β1 to LM-511. Cell migration assays using inhibitors for signal transduction and cytoskeletal organization showed that suppression of cell adhesion via the rho-associated protein kinase (ROCK) pathway promoted tumor cell migration on LM-511. Our results suggest that the ROCK pathway is involved in the transition from static to migratory cell behaviors on LM-511.
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: kikkawa@toyaku.ac.jp.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Harashima
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ikari
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
mesh_terms: D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016596:Vinculin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D039201:Integrin alpha3beta1; D039503:Integrin alpha6; D007797:Laminin; C119013:laminin 10; D016596:Vinculin; D054460:rho-Associated Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: Basement membrane; Cell adhesion; Cell migration; Integrin; Laminin