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.
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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)
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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
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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)
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