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Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination

机译:Twist1阳性上皮细胞在整个扩散过程中均保持黏附和增殖能力

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Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of?E-cadherin?leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor?Twist1?and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+?epithelium displayed extensive intercellular junctions, and Twist1–?luminal epithelial cells could still adhere to disseminating Twist1+?cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+?cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate.
机译:传播是细胞从多细胞组织分离并迁移的过程。上皮-间充质转变(EMT)以逐步的方式概念化传播,下调“ E-钙粘着蛋白”,导致细胞间连接的丧失,运动性的诱导,然后脱离上皮。有人认为,这种迁徙活动的获得与扩散是相互排斥的。我们先前开发了一种基于转录因子Twist1的可诱导表达的扩散测定法,并在这里利用它来表征细胞在扩散过程中粘附,增殖和迁移的时间和动力学。令人惊讶的是,Twist1 +?上皮显示出广泛的细胞间连接,并且Twist1 ??腔上皮细胞仍可以粘附在传播Twist1 +?细胞上。尽管在整个传播过程中都观察到了蛋白水解和增殖,但绝对不是必需的。最后,Twist1 +?细胞表现出混合迁移模式。它们的形态和核变形是变形虫细胞的特征,而它们的动态突起活性,细胞周围蛋白水解和迁移速度则是间充质细胞的典型特征。我们的数据表明,上皮细胞可以扩散,同时保留粘附和增殖的能力。

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