Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma

Fanghui Lu, Ying Chen, Chuntao Zhao, Haibo Wang, Danyang He, Lingli Xu, Jincheng Wang, Xuelian He, Yaqi Deng, Ellen E. Lu, Xue Liu, Ravinder Verma, Hong Bu, Rachid Drissi, Maryam Fouladi, Anat O. Stemmer-Rachamimov, Dennis Burns, Mei Xin, Joshua B. Rubin, El Mustapha BahassiPeter Canoll, Eric C. Holland, Q. Richard Lu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Here we identify mitotic Olig2-expressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate. Genome occupancy and expression profiling analyses reveal that Olig2 directly activates cell-proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrocyte precursor-correlated proneural toward an astroglia-associated gene expression pattern, manifest in downregulation of platelet-derived growth factor receptor-α and reciprocal upregulation of epidermal growth factor receptor (EGFR). Olig2 deletion further sensitizes glioma cells to EGFR inhibitors and extends the lifespan of animals. Thus, Olig2-orchestrated receptor signaling drives mitotic growth and regulates glioma phenotypic plasticity. Targeting Olig2 may circumvent resistance to EGFR-targeted drugs.

Original languageEnglish (US)
Pages (from-to)669-683
Number of pages15
JournalCancer Cell
Volume29
Issue number5
DOIs
StatePublished - May 9 2016

Fingerprint

Epidermal Growth Factor Receptor
Glioma
Phenotype
Growth
Neoplasms
Platelet-Derived Growth Factor Receptors
Oligodendroglia
Astrocytes
Carcinogenesis
Up-Regulation
Down-Regulation
Cell Proliferation
Genome
Gene Expression
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma. / Lu, Fanghui; Chen, Ying; Zhao, Chuntao; Wang, Haibo; He, Danyang; Xu, Lingli; Wang, Jincheng; He, Xuelian; Deng, Yaqi; Lu, Ellen E.; Liu, Xue; Verma, Ravinder; Bu, Hong; Drissi, Rachid; Fouladi, Maryam; Stemmer-Rachamimov, Anat O.; Burns, Dennis; Xin, Mei; Rubin, Joshua B.; Bahassi, El Mustapha; Canoll, Peter; Holland, Eric C.; Lu, Q. Richard.

In: Cancer Cell, Vol. 29, No. 5, 09.05.2016, p. 669-683.

Research output: Contribution to journalArticle

Lu, F, Chen, Y, Zhao, C, Wang, H, He, D, Xu, L, Wang, J, He, X, Deng, Y, Lu, EE, Liu, X, Verma, R, Bu, H, Drissi, R, Fouladi, M, Stemmer-Rachamimov, AO, Burns, D, Xin, M, Rubin, JB, Bahassi, EM, Canoll, P, Holland, EC & Lu, QR 2016, 'Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma', Cancer Cell, vol. 29, no. 5, pp. 669-683. https://doi.org/10.1016/j.ccell.2016.03.027
Lu, Fanghui ; Chen, Ying ; Zhao, Chuntao ; Wang, Haibo ; He, Danyang ; Xu, Lingli ; Wang, Jincheng ; He, Xuelian ; Deng, Yaqi ; Lu, Ellen E. ; Liu, Xue ; Verma, Ravinder ; Bu, Hong ; Drissi, Rachid ; Fouladi, Maryam ; Stemmer-Rachamimov, Anat O. ; Burns, Dennis ; Xin, Mei ; Rubin, Joshua B. ; Bahassi, El Mustapha ; Canoll, Peter ; Holland, Eric C. ; Lu, Q. Richard. / Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma. In: Cancer Cell. 2016 ; Vol. 29, No. 5. pp. 669-683.
@article{761fb507e74a4ac9834f11db6539047f,
title = "Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma",
abstract = "Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Here we identify mitotic Olig2-expressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate. Genome occupancy and expression profiling analyses reveal that Olig2 directly activates cell-proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrocyte precursor-correlated proneural toward an astroglia-associated gene expression pattern, manifest in downregulation of platelet-derived growth factor receptor-α and reciprocal upregulation of epidermal growth factor receptor (EGFR). Olig2 deletion further sensitizes glioma cells to EGFR inhibitors and extends the lifespan of animals. Thus, Olig2-orchestrated receptor signaling drives mitotic growth and regulates glioma phenotypic plasticity. Targeting Olig2 may circumvent resistance to EGFR-targeted drugs.",
author = "Fanghui Lu and Ying Chen and Chuntao Zhao and Haibo Wang and Danyang He and Lingli Xu and Jincheng Wang and Xuelian He and Yaqi Deng and Lu, {Ellen E.} and Xue Liu and Ravinder Verma and Hong Bu and Rachid Drissi and Maryam Fouladi and Stemmer-Rachamimov, {Anat O.} and Dennis Burns and Mei Xin and Rubin, {Joshua B.} and Bahassi, {El Mustapha} and Peter Canoll and Holland, {Eric C.} and Lu, {Q. Richard}",
year = "2016",
month = "5",
day = "9",
doi = "10.1016/j.ccell.2016.03.027",
language = "English (US)",
volume = "29",
pages = "669--683",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma

AU - Lu, Fanghui

AU - Chen, Ying

AU - Zhao, Chuntao

AU - Wang, Haibo

AU - He, Danyang

AU - Xu, Lingli

AU - Wang, Jincheng

AU - He, Xuelian

AU - Deng, Yaqi

AU - Lu, Ellen E.

AU - Liu, Xue

AU - Verma, Ravinder

AU - Bu, Hong

AU - Drissi, Rachid

AU - Fouladi, Maryam

AU - Stemmer-Rachamimov, Anat O.

AU - Burns, Dennis

AU - Xin, Mei

AU - Rubin, Joshua B.

AU - Bahassi, El Mustapha

AU - Canoll, Peter

AU - Holland, Eric C.

AU - Lu, Q. Richard

PY - 2016/5/9

Y1 - 2016/5/9

N2 - Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Here we identify mitotic Olig2-expressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate. Genome occupancy and expression profiling analyses reveal that Olig2 directly activates cell-proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrocyte precursor-correlated proneural toward an astroglia-associated gene expression pattern, manifest in downregulation of platelet-derived growth factor receptor-α and reciprocal upregulation of epidermal growth factor receptor (EGFR). Olig2 deletion further sensitizes glioma cells to EGFR inhibitors and extends the lifespan of animals. Thus, Olig2-orchestrated receptor signaling drives mitotic growth and regulates glioma phenotypic plasticity. Targeting Olig2 may circumvent resistance to EGFR-targeted drugs.

AB - Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Here we identify mitotic Olig2-expressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate. Genome occupancy and expression profiling analyses reveal that Olig2 directly activates cell-proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrocyte precursor-correlated proneural toward an astroglia-associated gene expression pattern, manifest in downregulation of platelet-derived growth factor receptor-α and reciprocal upregulation of epidermal growth factor receptor (EGFR). Olig2 deletion further sensitizes glioma cells to EGFR inhibitors and extends the lifespan of animals. Thus, Olig2-orchestrated receptor signaling drives mitotic growth and regulates glioma phenotypic plasticity. Targeting Olig2 may circumvent resistance to EGFR-targeted drugs.

UR - http://www.scopus.com/inward/record.url?scp=84975263198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975263198&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2016.03.027

DO - 10.1016/j.ccell.2016.03.027

M3 - Article

C2 - 27165742

AN - SCOPUS:84975263198

VL - 29

SP - 669

EP - 683

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -