Comprehensive protein tyrosine phosphatase mRNA profiling identifies new regulators in the progression of glioma

Acta Neuropathol Commun. 2016 Sep 1;4(1):96. doi: 10.1186/s40478-016-0372-x.

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.

Keywords: Astrocytoma; DUSP26; EGFR; Glioblastoma; IDH1; MTMR4; Malignancy; Oligodendroglioma; PTEN; PTP; PTPRM; PTPRN2; PTPRT; PTPRZ1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / pathology
  • CRISPR-Cas Systems
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioma / enzymology*
  • Glioma / genetics
  • Glioma / pathology
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Kaplan-Meier Estimate
  • Neoplasm Grading
  • PTEN Phosphohydrolase / deficiency
  • PTEN Phosphohydrolase / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • RNA, Messenger
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • PTEN protein, human