RUNX3 facilitates growth of Ewing sarcoma cells

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 - Dec 2014

Fingerprint Dive into the research topics of 'RUNX3 facilitates growth of Ewing sarcoma cells'. Together they form a unique fingerprint.

Cite this