Oncology Program and ICREA, Institute for Research in Biomedicine, Josep Samitier 1-5, 08028 Barcelona, Spain.
Cold Spring Harb Perspect Biol. 2012 Jan 1;4(1):a008227. doi: 10.1101/cshperspect.a008227.
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.
精确组织的建立和维持需要在不同细胞群体之间形成鲜明的边界。在成年期，隔离细胞群体的维持对于组织内稳态也是必需的，而细胞隔离的缺陷是肿瘤细胞转移扩散的基础。已经发现了三种机制可以解释细胞隔离和边界形成。第一种机制涉及到细胞间黏附的差异，即通过黏附蛋白介导的细胞间黏附在不同细胞群体之间形成界面张力。第二种机制涉及到细胞间信号诱导的肌动球蛋白介导的收缩，从而在边界处产生皮质张力。第三种机制是 Eph 受体和 Ephrins 的激活，通过触发 E-钙黏蛋白的裂解，触发细胞黏附的减少，通过调节肌动蛋白细胞骨架，触发细胞的排斥，从而阻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处起着至关重要的作用，而黏附蛋白或 Eph/ephrin 表达的改变与肿瘤转移有关。
