Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.
Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.
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DOI：
10.1038/onc.2016.498
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发表时间：
2017-06-22
期刊：
影响因子：
8
通讯作者：
Delattre O
中科院分区：
文献类型：
--
作者：
Franzetti GA;Laud-Duval K;van der Ent W;Brisac A;Irondelle M;Aubert S;Dirksen U;Bouvier C;de Pinieux G;Snaar-Jagalska E;Chavrier P;Delattre O
尤文肉瘤的特征在于嵌合EWSR 1-FLI 1转录因子的表达。蛋白质组学分析表明，EWSR 1-FLI 1表达的减少导致肌动蛋白细胞骨架的动态效应器和粘附过程的重大变化，从细胞到细胞到细胞-基质粘附的转变。这些变化与体内细胞迁移和侵袭潜力的急剧增加有关。重要的是，通过单细胞RT-ddPCR/免疫荧光分析评估的EWSR 1-FLI 1表达和通过EWSR 1-FLI 1下游靶点表达评估的活性在细胞系和肿瘤中是异质的，并且可以在EWSR 1-FLI 1高状态（特征在于高度活跃的细胞增殖）和EWSR 1-FLI 1低状态（其中细胞具有强烈的迁移倾向）之间的完全可逆过程中沿着时间波动，侵袭和转移。这种新的表型可塑性模型提出，显性癌基因表达水平的动态波动是其致癌潜力的内在特征。
Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.
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影响因子：
4.7
作者：
Kovar H;Alonso J;Aman P;Aryee DN;Ban J;Burchill SA;Burdach S;De Alava E;Delattre O;Dirksen U;Fourtouna A;Fulda S;Helman LJ;Herrero-Martin D;Hogendoorn PC;Kontny U;Lawlor ER;Lessnick SL;Llombart-Bosch A;Metzler M;Moriggl R;Niedan S;Potratz J;Redini F;Richter GH;Riedmann LT;Rossig C;Schäfer BW;Schwentner R;Scotlandi K;Sorensen PH;Staege MS;Tirode F;Toretsky J;Ventura S;Eggert A;Ladenstein R
通讯作者：
Ladenstein R
影响因子：
3.8
作者：
Kelm, JM;Timmins, NE;Nielsen, LK
通讯作者：
Nielsen, LK
影响因子：
11.2
作者：
Ban, Jozef;Aryee, Dave N. T.;Kovar, Heinrich
通讯作者：
Kovar, Heinrich
自动化的全动物生物成像分析用于人类癌症传播。
影响因子：
3.7
作者：
Ghotra VP;He S;de Bont H;van der Ent W;Spaink HP;van de Water B;Snaar-Jagalska BE;Danen EH
通讯作者：
Danen EH
DOI：
10.1158/1541-7786.mcr-13-0668
发表时间：
2014-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Krook MA;Nicholls LA;Scannell CA;Chugh R;Thomas DG;Lawlor ER
通讯作者：
Lawlor ER