Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition
Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition
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DOI：
10.1096/fj.09-151639
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Goldman, Robert D.
中科院分区：
文献类型：
--
作者：
Mendez, Melissa G.;Kojima, Shin-Ichiro;Goldman, Robert D.
波形蛋白被广泛用作胚胎发生和转移过程中发生的上皮间质转化（EMT）的标志物，但这种III型中间丝（IF）蛋白表达的功能意义知之甚少。使用形状因子分析和定量蛋白质印迹正常，转移，和波形蛋白空细胞系，我们表明，波形蛋白IFs（VIFs）的表达水平与间充质细胞的形状和运动行为。通过表达显性阴性突变体或通过用shRNA沉默波形蛋白（两者都不改变微管或微丝组装）引起的VIF重组导致间充质细胞采用上皮形状。显微注射波形蛋白或转染波形蛋白cDNA后，上皮细胞迅速采用与VIF组装一致的间充质形状。这些形状转变伴随着桥粒接触的丧失、细胞运动性的增加和粘着斑动力学的显著增加。我们的研究结果表明，VIFs在EMT期间发生的形状，粘附和运动性变化中起着主导作用。Mendez，M. G.，Kojima，S.-一、戈德曼河D.波形蛋白在上皮细胞向间充质细胞转化过程中诱导细胞形状、运动性和粘附性的变化。FASEB J.24，1838-1851（2010）。www.fasebj.org
Vimentin is used widely as a marker of the epithelial to mesenchymal transitions (EMTs) that take place during embryogenesis and metastasis, yet the functional implications of the expression of this type III intermediate filament (IF) protein are poorly understood. Using form factor analysis and quantitative Western blotting of normal, metastatic, and vimentin-null cell lines, we show that the level of expression of vimentin IFs (VIFs) correlates with mesenchymal cell shape and motile behavior. The reorganization of VIFs caused by expressing a dominant-negative mutant or by silencing vimentin with shRNA (neither of which alter microtubule or microfilament assembly) causes mesenchymal cells to adopt epithelial shapes. Following the microinjection of vimentin or transfection with vimentin cDNA, epithelial cells rapidly adopt mesenchymal shapes coincident with VIF assembly. These shape transitions are accompanied by a loss of desmosomal contacts, an increase in cell motility, and a significant increase in focal adhesion dynamics. Our results demonstrate that VIFs play a predominant role in the changes in shape, adhesion, and motility that occur during the EMT.-Mendez, M. G., Kojima, S.-I., Goldman, R. D. Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J. 24, 1838-1851 (2010). www.fasebj.org