TROY (TNFRSF19) is overexpressed in advanced glial tumors and promotes glioblastoma cell invasion via Pyk2-Rac1 signaling

Vincent M. Paulino, Zhongbo Yang, Jean Kloss, Matthew J. Ennis, Brock A. Armstrong, Joseph C Loftus, Nhan Tran

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A critical problem in the treatment of malignant gliomas is the extensive infiltration of individual tumor cells into adjacent brain tissues. This invasive phenotype severely limits all current therapies, and to date, no treatment is available to control the spread of this disease. Members of the tumor necrosis factor (TNF) ligand superfamily and their cognate receptors regulate various cellular responses including proliferation, migration, differentiation, and apoptosis. Specifically, the TNFRSF19/TROY gene encodes a type I cell surface receptor that is expressed on migrating or proliferating progenitor cells of the hippocampus, thalamus, and cerebral cortex. Here, we show that levels of TROY mRNA expression directly correlate with increasing glial tumor grade. Among malignant gliomas, TROYexpression correlates inversely with overall patient survival. In addition, we show that TROYoverexpression in glioma cells activates Rac1 signaling in a Pyk2-dependent manner to drive glioma cell invasion and migration. Pyk2 coimmunoprecipitates with the TROY receptor, and depletion of Pyk2 expression by short hairpin RNA interference oligonucleotides inhibits TROY-induced Rac1 activation and subsequent cellular migration. These findings position aberrant expression and/or signaling by TROY as a contributor, and possibly as a driver, of the malignant dispersion of glioma cells.

Original languageEnglish (US)
Pages (from-to)1558-1567
Number of pages10
JournalMolecular Cancer Research
Volume8
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Glioblastoma
Glioma
Neuroglia
Neoplasms
Tumor Necrosis Factors
Cell Surface Receptors
RNA Interference
Thalamus
Oligonucleotides
Cerebral Cortex
Small Interfering RNA
Cell Movement
Hippocampus
Stem Cells
Therapeutics
Apoptosis
Phenotype
Messenger RNA
Survival
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

TROY (TNFRSF19) is overexpressed in advanced glial tumors and promotes glioblastoma cell invasion via Pyk2-Rac1 signaling. / Paulino, Vincent M.; Yang, Zhongbo; Kloss, Jean; Ennis, Matthew J.; Armstrong, Brock A.; Loftus, Joseph C; Tran, Nhan.

In: Molecular Cancer Research, Vol. 8, No. 11, 11.2010, p. 1558-1567.

Research output: Contribution to journalArticle

Paulino, Vincent M. ; Yang, Zhongbo ; Kloss, Jean ; Ennis, Matthew J. ; Armstrong, Brock A. ; Loftus, Joseph C ; Tran, Nhan. / TROY (TNFRSF19) is overexpressed in advanced glial tumors and promotes glioblastoma cell invasion via Pyk2-Rac1 signaling. In: Molecular Cancer Research. 2010 ; Vol. 8, No. 11. pp. 1558-1567.
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