The Ewing's sarcoma fusion protein, EWS-FLI, binds Runx2 and blocks osteoblast differentiation.
The Ewing's sarcoma fusion protein, EWS-FLI, binds Runx2 and blocks osteoblast differentiation.
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DOI：
10.1002/jcb.22782
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
Li, Xiaodong;McGee-Lawrence, Meghan E.;Decker, Matthew;Westendorf, Jennifer J.
尤文氏肉瘤是一种侵袭性极强的骨和软组织圆形细胞肿瘤，多见于儿童和年轻人。这些肿瘤中的大多数具有t（11;22）易位并表达融合蛋白EWS-FLI。现代分子分析实验表明，尤因肿瘤起源于年轻个体的间充质前体。EWS-FLI改变间充质细胞的形态，并阻止谱系特化;然而，分化停滞的分子机制尚不清楚。我们最近发现，EWS-FLI结合Runx 2，成骨细胞分化的主要调节因子。在这份报告中，我们证明了EWS-FLI内的FLI序列负责与Runx 2的相互作用。EWS-FLI阻断多能祖细胞系中成骨细胞基因的表达，该祖细胞系需要Runx 2整合骨形态发生蛋白（Bmp）2信号传导，同时增加增殖并改变细胞形态。这些结果表明，EWS-FLI阻断Runx 2诱导间充质祖细胞的成骨细胞特化的能力。破坏Runx 2和EWS-FLI 1之间的相互作用可以促进肿瘤细胞的分化。
Ewing’s sarcomas are highly aggressive round cell tumors of bone and soft tissues that afflict children and young adults. The majority of these tumors harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Modern molecular profiling experiments indicate that Ewing’s tumors originate from mesenchymal precursors in young individuals. EWS-FLI alters the morphology of mesenchymal cells and prevents lineage specification; however, the molecular mechanisms for differentiation arrest are unclear. We recently showed that EWS-FLI binds Runx2, a master regulator of osteoblast differentiation. In this report, we demonstrate that FLI sequences within EWS-FLI are responsible for interactions with Runx2. EWS-FLI blocks the expression of osteoblastic genes in a multipotent progenitor cell line that requires Runx2 to integrate bone morphogenic protein (Bmp)2 signaling while increasing proliferation and altering cell morphology. These results demonstrate that EWS-FLI blocks the ability of Runx2 to induce osteoblast specification of a mesenchymal progenitor cell. Disrupting interactions between Runx2 and EWS-FLI1 may promote differentiation of the tumor cell.
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DOI：
10.1159/000151719
发表时间：
2009
期刊：
Cells, tissues, organs
影响因子：
--
作者：
Javed A;Afzal F;Bae JS;Gutierrez S;Zaidi K;Pratap J;van Wijnen AJ;Stein JL;Stein GS;Lian JB
通讯作者：
Lian JB
影响因子：
11.2
作者：
Kinsey M;Smith R;Iyer AK;McCabe ER;Lessnick SL
通讯作者：
Lessnick SL
影响因子：
5.6
作者：
Afzal, F;Pratap, J;Javed, A
通讯作者：
Javed, A
DOI：
10.1093/bfgp/ell015
发表时间：
2006-03-01
期刊：
Briefings in Functional Genomics & Proteomics
影响因子：
--
作者：
Law, Warren J.;Cann, Kendra L.;Hicks, Geoffrey G.
通讯作者：
Hicks, Geoffrey G.
影响因子：
4
作者：
Jensen, Eric D.;Niu, Lingling;Westendorf, Jennifer J.
通讯作者：
Westendorf, Jennifer J.