title: Loss of the protein-tyrosine phosphatase DEP-1/PTPRJ drives meningioma cell motility.
abstract: DEP-1/PTPRJ is a transmembrane protein-tyrosine phosphatase which has been proposed as a suppressor of epithelial tumors. We have found loss of heterozygosity (LOH) of the PTPRJ gene and loss of DEP-1 protein expression in a subset of human meningiomas. RNAi-mediated suppression of DEP-1 in DEP-1 positive meningioma cell lines caused enhanced motility and colony formation in semi-solid media. Cells devoid of DEP-1 exhibited enhanced signaling of endogenous platelet-derived growth factor (PDGF) receptors, and reduced paxillin phosphorylation upon seeding. Moreover, DEP-1 loss caused diminished adhesion to different matrices, and impaired cell spreading. DEP-1-deficient meningioma cells exhibited invasive growth in an orthotopic xenotransplantation model in nude mice, indicating that elevated motility translates into a biological phenotype in vivo. We propose that negative regulation of PDGF receptor signaling and positive regulation of adhesion signaling by DEP-1 cooperate in inhibition of meningioma cell motility, and possibly tumor invasiveness. These phenotypes of DEP-1 loss reveal functions of DEP-1 in adherent cells, and may be more generally relevant for tumorigenesis.
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Petermann
authors.forename: Daniela
authors.initials: D
authors.lastname: Haase
authors.forename: Andrea
authors.initials: A
authors.lastname: Wetzel
authors.forename: Kamal K
authors.initials: KK
authors.lastname: Balavenkatraman
authors.forename: Tencho
authors.initials: T
authors.lastname: Tenev
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Gührs
authors.forename: Sabrina
authors.initials: S
authors.lastname: Friedrich
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Frank-D
authors.initials: FD
authors.lastname: Böhmer
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D051419:Paxillin / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D051419:Paxillin; D034741:RNA, Small Interfering; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3