alexa The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial–mesenchymal transition (1997)
Oncology

Oncology

Journal of Integrative Oncology

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Abstract. Epithelial–mesenchymal transition (EMT) is an essential morphogenetic process during embryonic development. It can be induced in vitro by hepatocyte growth factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA and protein levels were increased transiently in FGF-1–treated NBT-II cells. Transient or stable transfection of Slug cDNA in NBT-II cells resulted in a striking disappearance of the desmosomal markers desmoplakin and desmoglein from cell–cell contact areas, mimicking the initial steps of FGF-1 or HGF/SFinduced EMT. Stable transfectant cells expressed Slug protein and were less epithelial, with increased cell spreading and cell–cell separation in subconfluent cultures. Interestingly, NBT-II cells transfected with antisense Slug cDNA were able to resist EMT induction by FGF-1 or even HGF/SF. This antisense effect was suppressed by retransfection with Slug sense cDNA. Our results indicate that Slug induces the first phase of growth factor–induced EMT, including desmosome dissociation, cell spreading, and initiation of cell separation. Moreover, the antisense inhibition experiments suggest that Slug is also necessary for EMT. Epithelial cells adhere to each other through specialized structures essential for the maintenance of epithelial organization and differentiation. Among these, structures linked to the cytokeratin intermediate filament network appear to provide the strongest and most resilient adhesion (12, 15). The core unit of such structures is the desmosome, which appears early during epithelial differentiation (13, 24, 30, 37). Desmoglein and desmocollins are desmosome-specific cadherins that mediate cell– cell binding (15, 34). They are part of a molecular complex

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This article was published in CiteSeerX and referenced in Journal of Integrative Oncology

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