RUNX3 facilitates growth of Ewing sarcoma cells.

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.

• Authors: 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
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 229 Issue 12 Pg. 2049-56 (Dec 2014) ISSN: 1097-4652 [Electronic] United States
• PMID: 24812032 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Core Binding Factor Alpha 3 Subunit
• EWS-FLI fusion protein
• Oncogene Proteins, Fusion
• Proto-Oncogene Protein c-fli-1
• RNA-Binding Protein EWS
• Runx3 protein, human

Topics

• Cell Differentiation (genetics)
• Cell Line, Tumor
• Core Binding Factor Alpha 3 Subunit (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms, Bone Tissue (genetics, pathology)
• Oncogene Proteins, Fusion (genetics, metabolism)
• Proto-Oncogene Protein c-fli-1 (genetics, metabolism)
• RNA-Binding Protein EWS (genetics, metabolism)
• Sarcoma, Ewing (genetics, pathology)