Cadherin Switch during EMT in Neural Crest Cells Leads to Contact Inhibition of Locomotion via Repolarization of Forces.
Cadherin Switch during EMT in Neural Crest Cells Leads to Contact Inhibition of Locomotion via Repolarization of Forces.
复制标题
神经嵴细胞 EMT 期间的钙粘蛋白开关通过力的复极化导致运动的接触抑制。
DOI：
10.1016/j.devcel.2015.06.012
复制
发表时间：
2015-08-24
影响因子：
11.8
通讯作者：
Mayor R
中科院分区：
文献类型：
--
作者：
Scarpa E;Szabó A;Bibonne A;Theveneau E;Parsons M;Mayor R
接触性运动抑制（Contact inhibition of motorization，CIL）是细胞与细胞接触后相互远离的过程，是恶性肿瘤侵袭和发育性迁移的重要机制。各种细胞类型表现出CIL，而其他细胞在碰撞后保持接触，并可能形成稳定的连接。为了研究是什么决定了这种差异行为，我们研究了神经嵴细胞，一种迁移性干细胞群，其侵袭性被比作癌症转移。通过比较迁移前和迁移的神经嵴细胞，我们表明，从E-到N-钙粘蛋白在EMT的开关是必不可少的收购CIL的行为。E-cadherin的丢失导致突起的复极化，通过p120和Rac 1，导致从细胞间张力到细胞-基质粘附的力的重新分布，从而破坏钙粘蛋白连接。这些数据提供了对有助于体内细胞中CIL的物理力的平衡的洞察。EMT期间神经嵴细胞获得运动的接触抑制（CIL）E-到N-钙粘蛋白开关控制CIL E-钙粘蛋白通过p120控制Rac 1依赖性突起来抑制CIL在CIL期间，力从细胞间连接重新分配到细胞基质细胞-细胞粘附在运动的接触抑制期间短暂形成。Scarpa等人显示了EMT时E-至N-钙粘蛋白转换控制CIL获取。E-钙粘蛋白缺失导致突起通过p120和Rac 1复极化，导致从细胞间张力到细胞-基质粘附的力重新分布，触发连接解体。
Contact inhibition of locomotion (CIL) is the process through which cells move away from each other after cell-cell contact, and it contributes to malignant invasion and developmental migration. Various cell types exhibit CIL, whereas others remain in contact after collision and may form stable junctions. To investigate what determines this differential behavior, we study neural crest cells, a migratory stem cell population whose invasiveness has been likened to cancer metastasis. By comparing pre-migratory and migratory neural crest cells, we show that the switch from E- to N-cadherin during EMT is essential for acquisition of CIL behavior. Loss of E-cadherin leads to repolarization of protrusions, via p120 and Rac1, resulting in a redistribution of forces from intercellular tension to cell-matrix adhesions, which break down the cadherin junction. These data provide insight into the balance of physical forces that contributes to CIL in cells in vivo. Neural crest cells acquire contact inhibition of locomotion (CIL) during EMT An E- to N-cadherin switch controls CIL E-cadherin represses CIL by controlling Rac1-dependent protrusions via p120 During CIL, forces are redistributed from intercellular junctions to cell matrix Cell-cell adhesions are transiently formed during contact inhibition of locomotion. Scarpa et al. show that an E- to N-cadherin switch controls CIL acquisition upon EMT. E-cadherin loss leads to repolarization of protrusions via p120 and Rac1, resulting in redistribution of forces from intercellular tension to cell-matrix adhesions, triggering junction disassembly.