Snail1 controls epithelial-mesenchymal lineage commitment in focal adhesion kinase-null embryonic cells.
Snail1 controls epithelial-mesenchymal lineage commitment in focal adhesion kinase-null embryonic cells.
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DOI：
10.1083/jcb.201105103
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发表时间：
2011-11-28
期刊：
影响因子：
--
通讯作者：
Weiss SJ
中科院分区：
文献类型：
--
作者：
Li XY;Zhou X;Rowe RG;Hu Y;Schlaepfer DD;Ilić D;Dressler G;Park A;Guan JL;Weiss SJ
FAK通过调控转录因子Snail 1促进小鼠胚胎细胞上皮-间质转化。小鼠胚胎细胞分离的粘着斑激酶（FAK）-空动物在胚胎第7.5天显示多个缺陷的粘着斑重塑，微管动力学，mechanotransduction，增殖，定向运动，和入侵。迄今为止，FAK调节细胞功能的能力主要归因于其对胚胎细胞群中转录后信号级联的控制。在本文中，我们表明，FAK出乎意料地发挥控制上皮间质转化（EMT）程序，使胚胎FAK-空细胞的上皮状态突出的E-钙粘蛋白，桥粒斑蛋白和细胞角蛋白的表达。FAK拯救重建FAK无效胚胎细胞的间充质特征，以通过细胞外信号相关激酶和Akt依赖性信号级联触发Snail1基因表达和Snail1蛋白稳定化来产生定向小鼠胚胎成纤维细胞。这些发现确定FAK作为一种新的调节Snail 1依赖EMT在胚胎细胞中，并建议在FAK −/−细胞行为的多重缺陷可以归因于这些细胞的上皮，而不是成纤维细胞，表型的不适当的承诺。
FAK promotes the epithelial–mesenchymal transition in mouse embryonic cells by regulating the transcription factor Snail1. Mouse embryonic cells isolated from focal adhesion kinase (FAK)–null animals at embryonic day 7.5 display multiple defects in focal adhesion remodeling, microtubule dynamics, mechanotransduction, proliferation, directional motility, and invasion. To date, the ability of FAK to modulate cell function has been ascribed largely to its control of posttranscriptional signaling cascades in this embryonic cell population. In this paper, we demonstrate that FAK unexpectedly exerts control over an epithelial–mesenchymal transition (EMT) program that commits embryonic FAK-null cells to an epithelial status highlighted by the expression of E-cadherin, desmoplakin, and cytokeratins. FAK rescue reestablished the mesenchymal characteristics of FAK-null embryonic cells to generate committed mouse embryonic fibroblasts via an extracellular signal–related kinase– and Akt-dependent signaling cascade that triggered Snail1 gene expression and Snail1 protein stabilization. These findings indentify FAK as a novel regulator of Snail1-dependent EMT in embryonic cells and suggest that multiple defects in FAK−/− cell behavior can be attributed to an inappropriate commitment of these cells to an epithelial, rather than fibroblastic, phenotype.
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影响因子：
7.3
作者：
Kim NH;Kim HS;Kim NG;Lee I;Choi HS;Li XY;Kang SE;Cha SY;Ryu JK;Na JM;Park C;Kim K;Lee S;Gumbiner BM;Yook JI;Weiss SJ
通讯作者：
Weiss SJ
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5.3
作者：
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作者：
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通讯作者：
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