Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Sci Rep. 2018 Mar 21;8(1):4986. doi: 10.1038/s41598-018-22940-3.
In this article, we explore a non-canonical form of collective cell migration, displayed by the metastatic murine mammary carcinoma cell line 4T1. We show here that in sparsely plated 4T1 cells, E-cadherin levels are moderately reduced (~50%), leading to the development of collective migration, whereby cells translocate in loose clusters, interconnected by thin membrane tethers. Knocking down E-cadherin blocked tether formation in these cells, leading to enhancement of migration rate and, at the same time, to suppression of lung metastases formation in vivo, and inhibition of infiltration into fibroblast monolayers ex vivo. These findings suggest that the moderate E-cadherin levels present in wild-type 4T1 cells play a key role in promoting cancer invasion and metastasis.
在本文中，我们探讨了一种非典型的细胞集体迁移形式，这种形式由转移性的小鼠乳腺肿瘤细胞系 4T1 展示。我们在这里表明，在稀疏接种的 4T1 细胞中，E-钙黏蛋白水平适度降低（约 50%），导致细胞发生集体迁移，细胞松散地聚集在一起，并通过薄的膜连丝连接。敲低 E-钙黏蛋白会阻止这些细胞中连接的形成，从而提高迁移速度，同时抑制体内肺转移的形成，并抑制体外向成纤维细胞单层的浸润。这些发现表明，野生型 4T1 细胞中存在的中等水平的 E-钙黏蛋白在促进癌症侵袭和转移方面发挥着关键作用。
