PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.
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.
Zheng
Hongwu
H
Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Ying
Haoqiang
H
Wiedemeyer
Ruprecht
R
Yan
Haiyan
H
Quayle
Steven N
SN
Ivanova
Elena V
EV
Paik
Ji-Hye
JH
Zhang
Hailei
H
Xiao
Yonghong
Y
Perry
Samuel R
SR
Hu
Jian
J
Vinjamoori
Anant
A
Gan
Boyi
B
Sahin
Ergun
E
Chheda
Milan G
MG
Brennan
Cameron
C
Wang
Y Alan
YA
Hahn
William C
WC
Chin
Lynda
L
DePinho
Ronald A
RA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000502:physiology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D016601:RNA-Binding Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C485426:Plagl2 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051153:Wnt Proteins