RUNX3 facilitates growth of Ewing sarcoma cells

Krista L. Bledsoe, Meghan Elizabeth McGee Lawrence, Emily T. Camilleri, Xiaoke Wang, Scott M. Riester, Andre J. van Wijnen, Andre M. Oliveira, Jennifer J. Westendorf

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma.

Original languageEnglish (US)
Pages (from-to)2049-2056
Number of pages8
JournalJournal of Cellular Physiology
Volume229
Issue number12
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Ewing's Sarcoma
Tumors
Bone
Transcription Factors
Pediatrics
Osteoblasts
Transcription
Growth
Ports and harbors
Agar
Assays
Genes
Cells
Genetic Translocation
Proteins
Oncogenes
Osteogenesis
Neoplasms
Bone and Bones
Cell Line

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Bledsoe, K. L., McGee Lawrence, M. E., Camilleri, E. T., Wang, X., Riester, S. M., van Wijnen, A. J., ... Westendorf, J. J. (2014). RUNX3 facilitates growth of Ewing sarcoma cells. Journal of Cellular Physiology, 229(12), 2049-2056. https://doi.org/10.1002/jcp.24663

RUNX3 facilitates growth of Ewing sarcoma cells. / Bledsoe, Krista L.; McGee Lawrence, Meghan Elizabeth; Camilleri, Emily T.; Wang, Xiaoke; Riester, Scott M.; van Wijnen, Andre J.; Oliveira, Andre M.; Westendorf, Jennifer J.

In: Journal of Cellular Physiology, Vol. 229, No. 12, 01.01.2014, p. 2049-2056.

Research output: Contribution to journalArticle

Bledsoe, KL, McGee Lawrence, ME, Camilleri, ET, Wang, X, Riester, SM, van Wijnen, AJ, Oliveira, AM & Westendorf, JJ 2014, 'RUNX3 facilitates growth of Ewing sarcoma cells', Journal of Cellular Physiology, vol. 229, no. 12, pp. 2049-2056. https://doi.org/10.1002/jcp.24663
Bledsoe KL, McGee Lawrence ME, Camilleri ET, Wang X, Riester SM, van Wijnen AJ et al. RUNX3 facilitates growth of Ewing sarcoma cells. Journal of Cellular Physiology. 2014 Jan 1;229(12):2049-2056. https://doi.org/10.1002/jcp.24663
Bledsoe, Krista L. ; McGee Lawrence, Meghan Elizabeth ; Camilleri, Emily T. ; Wang, Xiaoke ; Riester, Scott M. ; van Wijnen, Andre J. ; Oliveira, Andre M. ; Westendorf, Jennifer J. / RUNX3 facilitates growth of Ewing sarcoma cells. In: Journal of Cellular Physiology. 2014 ; Vol. 229, No. 12. pp. 2049-2056.
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