title: Differential role of proline-rich tyrosine kinase 2 and focal adhesion kinase in determining glioblastoma migration and proliferation.
abstract: The propensity of malignant gliomas to invade surrounding brain tissue contributes to poor clinical outcome. Integrin-mediated adhesion to extracellular matrix regulates the migration and proliferation of many cell types, but its role in glioma progression is undefined. We investigated the role of the cytoplasmic tyrosine kinases FAK and Pyk2, potential integrin effectors, in the phenotypic determination of four different human glioblastoma cell lines. While FAK expression was similar between the four cell lines, increased FAK activity correlated with high proliferation and low migratory rates. In contrast, Pyk2 activity was significantly increased in migratory cell lines and depressed in proliferative cell lines. Overexpression of Pyk2 stimulated migration, whereas FAK overexpression inhibited cell migration and stimulated cellular proliferation. These data suggest that FAK and Pyk2 function as important signaling effectors in gliomas and indicate that their differential regulation may be determining factors in the temporal development of proliferative or migrational phenotypes.
authors.affiliation: Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lipinski
authors.forename: Nhan L
authors.initials: NL
authors.lastname: Tran
authors.forename: Curtis
authors.initials: C
authors.lastname: Bay
authors.forename: Jean
authors.initials: J
authors.lastname: Kloss
authors.forename: Wendy S
authors.initials: WS
authors.lastname: McDonough
authors.forename: Christian
authors.initials: C
authors.lastname: Beaudry
authors.forename: Michael E
authors.initials: ME
authors.lastname: Berens
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Loftus
mesh_terms: D001932:Brain Neoplasms; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma; D006801:Humans; D010641:Phenotype; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human