title: Comprehensive protein tyrosine phosphatase mRNA profiling identifies new regulators in the progression of glioma.
abstract: The infiltrative behavior of diffuse gliomas severely reduces therapeutic potential of surgical resection and radiotherapy, and urges for the identification of new drug-targets affecting glioma growth and migration. To address the potential role of protein tyrosine phosphatases (PTPs), we performed mRNA expression profiling for 91 of the 109 known human PTP genes on a series of clinical diffuse glioma samples of different grades and compared our findings with in silico knowledge from REMBRANDT and TCGA databases. Overall PTP family expression levels appeared independent of characteristic genetic aberrations associated with lower grade or high grade gliomas. Notably, seven PTP genes (DUSP26, MTMR4, PTEN, PTPRM, PTPRN2, PTPRT and PTPRZ1) were differentially expressed between grade II-III gliomas and (grade IV) glioblastomas. For DUSP26, PTEN, PTPRM and PTPRT, lower expression levels correlated with poor prognosis, and overexpression of DUSP26 or PTPRT in E98 glioblastoma cells reduced tumorigenicity. Our study represents the first in-depth analysis of PTP family expression in diffuse glioma subtypes and warrants further investigations into PTP-dependent signaling events as new entry points for improved therapy.
authors: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands.
authors: Annika M
authors: AM
authors: Bourgonje
authors: Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Kiek
authors: K
authors: Verrijp
authors: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands.
authors: Jan T G
authors: JT
authors: Schepens
authors: Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Anna C
authors: AC
authors: Navis
authors: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands.
authors: Jolanda A F
authors: JA
authors: Piepers
authors: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands.
authors: Chantal B C
authors: CB
authors: Palmen
authors: Merck Serono S.A, Geneva, Switzerland.
authors: Monique
authors: M
authors: van den Eijnden
authors: Merck Serono S.A, Geneva, Switzerland.
authors: Rob
authors: R
authors: Hooft van Huijsduijnen
authors: Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Pieter
authors: P
authors: Wesseling
authors: Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: William P J
authors: WP
authors: Leenders
authors: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands. wiljanjaj.hendriks@radboudumc.nl.
authors: Wiljan J A J
authors: WJ
authors: Hendriks
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D064113:CRISPR-Cas Systems; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D060787:Neoplasm Grading; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Astrocytoma; DUSP26; EGFR; Glioblastoma; IDH1; MTMR4; Malignancy; Oligodendroglioma; PTEN; PTP; PTPRM; PTPRN2; PTPRT; PTPRZ1