PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas

Hongwu Zheng, Haoqiang Ying, Ruprecht Wiedemeyer, Haiyan Yan, Steven N. Quayle, Elena V. Ivanova, Ji Hye Paik, Hailei Zhang, Yonghong Xiao, Samuel R. Perry, Jian Hu, Anant Vinjamoori, Boyi Gan, Ergun Sahin, Milan G. Chheda, Cameron Brennan, Y. Alan Wang, William C. Hahn, Lynda Chin, Ronald A. DePinho

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

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/β-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.

Original languageEnglish
Pages (from-to)497-509
Number of pages13
JournalCancer Cell
Volume17
Issue number5
DOIs
StatePublished - May 18 2010

Keywords

  • CELLCYCLE
  • SIGNALING
  • STEMCELL

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