N-cadherin as a key regulator of collective cell migration in a 3D environment.

N-cadherin as a key regulator of collective cell migration in a 3D environment.
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DOI:
10.4161/cam.21766
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发表时间:
2012-11
影响因子:
3.2
通讯作者:
Yamada S
Yamada S
中科院分区:
生物学3区
文献类型:
--
作者:
Shih W;Yamada S

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细胞迁移是正常发育过程和疾病发展的关键步骤。通常,迁移细胞与邻近细胞相互作用并保持联系。然而,到目前为止,细胞间黏附在细胞迁移中的确切作用还不是很清楚。通常在侵袭性癌症中,N-钙粘附素显著上调,然而,当这些高度移动的细胞被电镀在坚硬的2D底物上时,细胞与细胞之间的黏附有限。但是,3D矩阵中的相同细胞以多细胞簇的形式迁移。这一新的观察结果表明,N-钙粘附素介导的细胞-细胞黏附支持更具生理相关性的3D基质中迁移细胞之间的细胞相互作用,但不支持2D基质上的细胞相互作用。虽然N-钙粘蛋白是神经突触不可或缺的一部分,但在转化的上皮细胞中,N-钙粘附素的异位表达在启动亲迁移信号和提供强大而灵活的细胞内聚力方面发挥着同样重要的作用,这是细胞在3D基质中持续迁移所必需的。用于研究细胞间相互作用的三维细胞迁移分析揭示了N-钙粘蛋白在多细胞迁移中的作用,并揭示了对细胞迁移依赖的正常和病理过程的新见解。
Cell migration is a critical step of normal developmental processes and disease progression. Often, migrating cells interact and maintain contact with neighboring cells. However, the precise roles of cell-cell adhesion in cell migration have thus far been poorly defined. Often in aggressive cancers, N-cadherin is prominently upregulated, yet, these highly motile cells have limited cell-cell adhesion when plated on a stiff 2D substrate. But, the same cells in a 3D matrix migrate as a multicellular cluster. This new observation suggests that N-cadherin-mediated cell-cell adhesion supports cell interactions between migrating cells in a more physiologically relevant 3D matrix, but not on a 2D substrate. While N-cadherin is an integral part of neural synapses, the ectopic expression of N-cadherin in transformed epithelial cells plays an equally important part in initiating pro-migratory signaling, and providing strong yet flexible cell cohesion essential for persistent cell migration in a 3D matrix. The 3D cell migration analysis for studying cell-to-cell interactions exposes the roles of N-cadherin in multicellular migration, and reveals novel insights into cell migration-dependent normal and pathological processes.
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