RUNX3 facilitates growth of Ewing sarcoma cells.
RUNX3 facilitates growth of Ewing sarcoma cells.
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DOI：
10.1002/jcp.24663
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发表时间：
2014-12
影响因子：
5.6
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
Bledsoe, Krista L.;McGee-Lawrence, Meghan E.;Camilleri, Emily T.;Wang, Xiaoke;Riester, Scott M.;van Wijnen, Andre J.;Oliveira, Andre M.;Westendorf, Jennifer J.
尤文氏肉瘤是一种侵袭性的儿童小圆细胞肿瘤，主要发生在骨骼。大约85%的尤文氏肉瘤含有EWS/FLI融合蛋白，这是由染色体易位引起的，t（11:22）。EWS/FLI与许多谱系必需的转录因子相互作用，维持间充质祖细胞处于未分化状态。我们之前发现EWS/FLI结合成骨转录因子RUNX2并阻止成骨细胞分化。在本研究中，我们研究了另一种runt结构域蛋白RUNX3在Ewing肉瘤中的作用。RUNX3参与间充质源性骨形成，是一种依赖于环境的肿瘤抑制因子和致癌基因。在所有检查的Ewing肉瘤细胞中均检测到RUNX3，而仅在73%的标本中检测到RUNX2。与RUNX2一样，RUNX3通过其Runt结构域与EWS/FLI结合。EWS/FLI阻止RUNX3激活runx应答报告基因p6OSE2的转录。稳定抑制RUNX3在Ewing肉瘤细胞系A673中的表达，在锚定独立软琼脂实验中延迟了菌落生长，逆转了EWS/ fli应答基因的表达。这些结果表明RUNX3在Ewing肉瘤中的重要作用。
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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