Open AccessLoss of the Protein‐Tyrosine Phosphatase DEP‐1/PTPRJ Drives Meningioma Cell Motility
Author(s) -
Petermann Astrid,
Haase Daniela,
Wetzel Andrea,
Balavenkatraman Kamal K.,
Tenev Tencho,
Gührs KarlHeinz,
Friedrich Sabrina,
Nakamura Makoto,
Mawrin Christian,
Böhmer FrankD.
Publication year - 2011
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2010.00464.x
Subject(s) - motility , protein tyrosine phosphatase , microbiology and biotechnology , biology , cancer research , carcinogenesis , cell growth , phenotype , tyrosine phosphorylation , signal transduction , biochemistry , gene
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.