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

Hongwu Zheng; Haoqiang Ying; Ruprecht Wiedemeyer; Haiyan Yan; Steven N. Quayle; Elena V. Ivanova; Ji Hye Paik; Hailei Zhang; Yonghong Xiao; Samuel R. Perry; Jian Hu; Anant Vinjamoori; Boyi Gan; Ergun Sahin; Milan G. Chheda; Cameron Brennan; Y. Alan Wang; William C. Hahn; Lynda Chin; Ronald A. DePinho

doi:10.1016/j.ccr.2010.03.020

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

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

Genomic Medicine

Research output: Contribution to journal › Article › peer-review

212 Scopus citations

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.

Original language	English (US)
Pages (from-to)	497-509
Number of pages	13
Journal	Cancer cell
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2010.03.020
State	Published - May 18 2010

Keywords

CELLCYCLE
SIGNALING
STEMCELL

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2010.03.020

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Zheng, H., Ying, H., Wiedemeyer, R., Yan, H., Quayle, S. N., Ivanova, E. V., Paik, J. H., Zhang, H., Xiao, Y., Perry, S. R., Hu, J., Vinjamoori, A., Gan, B., Sahin, E., Chheda, M. G., Brennan, C., Wang, Y. A., Hahn, W. C., Chin, L., & 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

Zheng, H, Ying, H, Wiedemeyer, R, Yan, H, Quayle, SN, Ivanova, EV, Paik, JH, Zhang, H, Xiao, Y, Perry, SR, Hu, J, Vinjamoori, A, Gan, B, Sahin, E, Chheda, MG, Brennan, C, Wang, YA, Hahn, WC, Chin, L & DePinho, RA 2010, 'PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas', Cancer cell, vol. 17, no. 5, pp. 497-509. https://doi.org/10.1016/j.ccr.2010.03.020

@article{4a1dc430aa8747f79b7d1f7c575c9a44,

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/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.",

keywords = "CELLCYCLE, SIGNALING, STEMCELL",

author = "Hongwu Zheng and Haoqiang Ying and Ruprecht Wiedemeyer and Haiyan Yan and Quayle, {Steven N.} and Ivanova, {Elena V.} and Paik, {Ji Hye} and Hailei Zhang and Yonghong Xiao and Perry, {Samuel R.} and Jian Hu and Anant Vinjamoori and Boyi Gan and Ergun Sahin and Chheda, {Milan G.} and Cameron Brennan and Wang, {Y. Alan} and Hahn, {William C.} and Lynda Chin and DePinho, {Ronald A.}",

note = "Funding Information: We thank S. Zhou and S. Jiang for excellent mouse husbandry and care. H.Z. was supported by the Helen Hay Whitney Foundation. H.Y. is supported by the American Brain Tumor Association. J.H.P was supported by the Damon Runyon Cancer Research Foundation. R.W. is supported by a Mildred Scheel Fellowship (Deutsche Krebshilfe), and S.N.Q. is supported by a fellowship from the Canadian Institutes of Health Research. Grant support comes from the Goldhirsh Foundation (R.A.D.), the Ben and Catherine Ivy Foundation (W.C.H., L.C., and R.A.D.), the Multiple Myeloma Research Foundation (Y.A.W.), and National Institutes of Health grants RO1CA99041 (L.C.), 5P01CA95616 (W.C.H., L.C., and R.A.D.), 1RC2CA148268-01 (W.C.H., L.C., and R.A.D.), and 1RC2CA148222-01 (R.A.D.). R.A.D. is an American Cancer Society Research Professor and is supported by the Robert A. and Renee E. Belfer Foundation for Innovative Cancer Science. ",

year = "2010",

month = may,

day = "18",

doi = "10.1016/j.ccr.2010.03.020",

language = "English (US)",

volume = "17",

pages = "497--509",

journal = "Cancer cell",

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publisher = "Cell Press",

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T1 - PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas

AU - Zheng, Hongwu

AU - Ying, Haoqiang

AU - Wiedemeyer, Ruprecht

AU - Yan, Haiyan

AU - Quayle, Steven N.

AU - Ivanova, Elena V.

AU - Paik, Ji Hye

AU - Zhang, Hailei

AU - Xiao, Yonghong

AU - Perry, Samuel R.

AU - Hu, Jian

AU - Vinjamoori, Anant

AU - Gan, Boyi

AU - Sahin, Ergun

AU - Chheda, Milan G.

AU - Brennan, Cameron

AU - Wang, Y. Alan

AU - Hahn, William C.

AU - Chin, Lynda

AU - DePinho, Ronald A.

N1 - Funding Information: We thank S. Zhou and S. Jiang for excellent mouse husbandry and care. H.Z. was supported by the Helen Hay Whitney Foundation. H.Y. is supported by the American Brain Tumor Association. J.H.P was supported by the Damon Runyon Cancer Research Foundation. R.W. is supported by a Mildred Scheel Fellowship (Deutsche Krebshilfe), and S.N.Q. is supported by a fellowship from the Canadian Institutes of Health Research. Grant support comes from the Goldhirsh Foundation (R.A.D.), the Ben and Catherine Ivy Foundation (W.C.H., L.C., and R.A.D.), the Multiple Myeloma Research Foundation (Y.A.W.), and National Institutes of Health grants RO1CA99041 (L.C.), 5P01CA95616 (W.C.H., L.C., and R.A.D.), 1RC2CA148268-01 (W.C.H., L.C., and R.A.D.), and 1RC2CA148222-01 (R.A.D.). R.A.D. is an American Cancer Society Research Professor and is supported by the Robert A. and Renee E. Belfer Foundation for Innovative Cancer Science.

PY - 2010/5/18

Y1 - 2010/5/18

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - SIGNALING

KW - STEMCELL

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U2 - 10.1016/j.ccr.2010.03.020

DO - 10.1016/j.ccr.2010.03.020

M3 - Article

C2 - 20478531

AN - SCOPUS:77952107413

SN - 1535-6108

VL - 17

SP - 497

EP - 509

JO - Cancer cell

JF - Cancer cell

IS - 5

ER -

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

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