PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • DNA-Binding Proteins
  • Glioblastoma
  • RNA-Binding Proteins
  • Signal Transduction
  • Stem Cells
  • Transcription Factors
  • Wnt Proteins

abstract

  • A hallmark feature of glioblastoma is its strong self-renewal potential and immature differentiation state, which contributes to its plasticity and therapeutic resistance. Here, integrated genomic and biological analyses identified PLAGL2 as a potent protooncogene targeted for amplification/gain in malignant gliomas. Enhanced PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell differentiation while promoting their self-renewal capacity upon differentiation induction. Transcriptome analysis revealed that these differentiation-suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling. Inhibition of Wnt signaling partially restores PLAGL2-expressing NSC differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics in malignant cells.

publication date

  • May 18, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2900858

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2010.03.020

PubMed ID

  • 20478531

Additional Document Info

start page

  • 497

end page

  • 509

volume

  • 17

number

  • 5