title: 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.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, Minnesota.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Bledsoe
authors.forename: Meghan E
authors.initials: ME
authors.lastname: McGee-Lawrence
authors.forename: Emily T
authors.initials: ET
authors.lastname: Camilleri
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Wang
authors.forename: Scott M
authors.initials: SM
authors.lastname: Riester
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Andre M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018213:Neoplasms, Bone Tissue / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; C493729:Runx3 protein, human