Molecular Mechanisms of Cell Segregation and Boundary Formation in Development and Tumorigenesis
Molecular Mechanisms of Cell Segregation and Boundary Formation in Development and Tumorigenesis
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DOI：
10.1101/cshperspect.a008227
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发表时间：
2012-01-01
影响因子：
7.2
通讯作者：
Wilkinson, David G.
中科院分区：
文献类型：
--
作者：
Batlle, Eduard;Wilkinson, David G.
建立和维持精确组织的组织需要在不同的细胞群体之间形成清晰的边界。成人的组织内稳态也需要维持分离的细胞群体，而分离的缺陷是肿瘤细胞转移扩散的基础。细胞分离和边界形成的三种机制已经被揭示。第一个涉及钙粘附素介导的细胞-细胞黏附的差异，这种黏附在不同细胞群体之间的边界建立了界面张力。第二种机制包括通过细胞间信号诱导肌动球蛋白介导的收缩，从而在交界处产生皮质张力。第三，Eph受体和肾上腺素的激活既可以通过触发E-钙粘附素的切割而导致粘附性降低，又可以通过调节肌动蛋白细胞骨架而导致细胞排斥，从而防止细胞群体之间的混合。这些机制在发育过程中的不同边界上发挥着关键作用，钙粘素或Eph/EPhin表达的变化与肿瘤转移有关。
The establishment and maintenance of precisely organized tissues requires the formation of sharp borders between distinct cell populations. The maintenance of segregated cell populations is also required for tissue homeostasis in the adult, and deficiencies in segregation underlie the metastatic spreading of tumor cells. Three classes of mechanisms that underlie cell segregation and border formation have been uncovered. The first involves differences in cadherin-mediated cell-cell adhesion that establishes interfacial tension at the border between distinct cell populations. A second mechanism involves the induction of actomyosin-mediated contraction by intercellular signaling, such that cortical tension is generated at the border. Third, activation of Eph receptors and ephrins can lead to both decreased adhesion by triggering cleavage of E-cadherin, and to repulsion of cells by regulation of the actin cytoskeleton, thus preventing intermingling between cell populations. These mechanisms play crucial roles at distinct boundaries during development, and alterations in cadherin or Eph/ephrin expression have been implicated in tumor metastasis.