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

43 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma'. Together they form a unique fingerprint.

  • Cite this

    Lu, F., Chen, Y., Zhao, C., Wang, H., He, D., Xu, L., Wang, J., He, X., Deng, Y., Lu, E. E., Liu, X., Verma, R., Bu, H., Drissi, R., Fouladi, M., Stemmer-Rachamimov, A. O., Burns, D., Xin, M., Rubin, J. B., ... Lu, Q. R. (2016). Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma. Cancer Cell, 29(5), 669-683. https://doi.org/10.1016/j.ccell.2016.03.027