C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells

Jamie D. Gardiner, Lisa M. Abegglen, Xiaomeng Huang, Bryce E. Carter, Elizabeth A. Schackmann, Marcus Stucki, Christian N. Paxton, R Randall, James F. Amatruda, Angelica R. Putnam, Heinrich Kovar, Stephen L. Lessnick, Joshua D. Schiffman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance.

Original languageEnglish (US)
Pages (from-to)26013-26026
Number of pages14
JournalOncotarget
Volume8
Issue number16
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • ALDH1A1
  • Biomarker
  • C/EBPβ
  • Chemoresistance
  • Ewing sarcoma

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Gardiner, J. D., Abegglen, L. M., Huang, X., Carter, B. E., Schackmann, E. A., Stucki, M., Paxton, C. N., Randall, R., Amatruda, J. F., Putnam, A. R., Kovar, H., Lessnick, S. L., & Schiffman, J. D. (2017). C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells. Oncotarget, 8(16), 26013-26026. https://doi.org/10.18632/oncotarget.14847