title: PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.
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/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.
authors.affiliation: Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zheng
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Ying
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Wiedemeyer
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yan
authors.forename: Steven N
authors.initials: SN
authors.lastname: Quayle
authors.forename: Elena V
authors.initials: EV
authors.lastname: Ivanova
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Paik
authors.forename: Hailei
authors.initials: H
authors.lastname: Zhang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xiao
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Perry
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Anant
authors.initials: A
authors.lastname: Vinjamoori
authors.forename: Boyi
authors.initials: B
authors.lastname: Gan
authors.forename: Ergun
authors.initials: E
authors.lastname: Sahin
authors.forename: Milan G
authors.initials: MG
authors.lastname: Chheda
authors.forename: Cameron
authors.initials: C
authors.lastname: Brennan
authors.forename: Y Alan
authors.initials: YA
authors.lastname: Wang
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; C485426:Plagl2 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051153:Wnt Proteins