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