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

被引：233

作者：

Zheng, Hongwu ^{[1
,2
,3
,4
]}

Ying, Haoqiang ^{[1
,2
,3
,4
]}

Wiedemeyer, Ruprecht ^{[1
,2
]}

Yan, Haiyan ^{[1
,2
]}

Quayle, Steven N. ^{[1
,2
,3
,4
]}

Ivanova, Elena V. ^{[1
,2
]}

Paik, Ji-Hye ^{[1
,2
,3
,4
]}

Zhang, Hailei ^{[1
,2
]}

Xiao, Yonghong ^{[1
,2
]}

Perry, Samuel R. ^{[1
,2
]}

Hu, Jian ^{[1
,2
,3
,4
]}

Vinjamoori, Anant ^{[2
]}

Gan, Boyi ^{[1
,2
,3
,4
]}

Sahin, Ergun ^{[1
,2
,3
,4
]}

Chheda, Milan G. ^{[2
,3
,6
,7
]}

Brennan, Cameron ^{[8
,9
]}

Wang, Y. Alan ^{[1
,2
]}

Hahn, William C. ^{[2
,3
,7
]}

Chin, Lynda ^{[1
,2
,3
,4
,5
,7
]}

DePinho, Ronald A. ^{[1
,2
,3
,4
]}

机构：

[1] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02129 USA

[7] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA

[9] Weill Cornell Med Coll, Dept Neurosurg, New York, NY 10065 USA

来源：

CANCER CELL | 2010年 / 17卷 / 05期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

TUMOR-INITIATING CELLS; BETA-CATENIN; HUMAN GLIOBLASTOMA; SELF-RENEWAL; SPORADIC MEDULLOBLASTOMAS; PATHWAY ACTIVATION; PROGENITOR CELLS; BRAIN-TUMORS; CANCER-CELLS; DISEASE;

D O I：

10.1016/j.ccr.2010.03.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：497 / 509

页数：13

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