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SHR Neuro Krebs Kardio Lipid

Bernhart, E; Damm, S; Wintersperger, A; DeVaney, T; Zimmer, A; Raynham, T; Ireson, C; Sattler, W.
Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro.
Exp Cell Res. 2013; 319(13):2037-2048 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Damm Sabine
Devaney Trevor
Sattler Wolfgang
Wintersperger Andrea
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Number of Figures: 6
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Abstract:
Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoated or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun(S73) phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Copyright © 2013 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Brain Neoplasms - genetics
Cell Line, Tumor -
Cell Movement - drug effects
Drug Evaluation, Preclinical -
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Glioblastoma - genetics
Humans -
Lysophospholipids - pharmacology
MAP Kinase Signaling System - drug effects
Neoplasm Invasiveness -
Protein Kinase Inhibitors - pharmacology
Protein Kinases - genetics
Pyrimidines - pharmacology
RNA Interference - physiology
RNA, Small Interfering - pharmacology
Sphingosine - analogs & derivatives

Find related publications in this database (Keywords)
Glioblastoma
Sphingosine-l-phosphate
PRKD2
MAPK C-Jun
Invasion
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