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

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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. © 2010 Elsevier Inc. All rights reserved.

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Zheng, H., Ying, H., Wiedemeyer, R., Yan, H., Quayle, S. N., Ivanova, E. V., … DePinho, R. A. (2010). PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas. Cancer Cell, 17(5), 497–509. https://doi.org/10.1016/j.ccr.2010.03.020

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