title: Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells.
abstract: Adenoid cystic carcinoma (AdCC) cell lines (ACCS and ACCT) showed higher migration responses and adhesion to the extracellular matrix (ECM), especially types I and IV collagen, than did the oral squamous cell carcinoma (SCC) lines (NA and TF). The response to collagens was largely and exclusively inhibited by anti-alpha(2) integrin antibody. Moreover, AdCC cell lines expressed higher surface levels of urokinase-type plasminogen activator receptor (uPAR) than did SCC cell lines. When AdCC cells were plated on collagen, the surface level of uPAR was increased, and numerous focal adhesions consisting of uPAR, vinculin, and paxillin were assembled; whereas collagen-stimulated SCC cell counterparts or AdCC cells plated on other types of ECM, such as fibronectin, failed to assemble such definite focal adhesions. In order to elucidate the association of uPAR with collagen-induced events, an ACCS-AS cell line transfected with a vector expressing antisense uPAR RNA was established and shown to have reduced uPAR (about 10% that of parental ACCS at both the protein and mRNA levels). ACCS-AS showed a strong reduction of collagen-stimulated migration and focal adhesion assembly of alpha(2) integrin, vinculin, and paxillin. These findings suggest that AdCC has a proclivity for migrating to types I and IV collagens due to the overexpression of uPAR, which plays a key role in focal adhesion assembly and migration.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Samah
authors.initials: S
authors.lastname: Abu-Ali
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
authors.forename: Miho
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toru
authors.initials: T
authors.lastname: Shiratsuchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ikari
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Seki
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Hiraki
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Matsuki
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Shirasuna
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000494:pharmacology; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D016372:RNA, Antisense; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016596:Vinculin / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D039421:Integrin alpha2; C524898:PLAUR protein, human; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016596:Vinculin