病理观察表明，癌细胞经常以集体而不是单个细胞迁移的方式侵入周围正常组织。然而，控制集体细胞迁移的一般原则仍有待发现。与单个细胞迁移不同，我们证明Notch-1激活降低了集体细胞的速度和距离。特别是，Notch-1 激活诱导细胞细胞骨架重塑，增强细胞间连接和细胞基质粘附。从机制上讲，Notch-1 激活阻止了 GSK-3β 的磷酸化和细胞质游离 β-catenin 易位到细胞核，从而增加了 E-cadherin 表达和紧密的细胞间连接。此外，Notch-1信号还激活RhoA/ROCK通路，促进F-肌动蛋白的重组和肌球蛋白产生的收缩力。此外，Notch-1 激活增加了细胞与细胞外基质的粘附，从而抑制了集体细胞迁移。这些发现强调了细胞粘附和细胞-细胞连接有助于集体细胞迁移，并为癌细胞恶性肿瘤中 Notch-1 信号通路的调节机制提供了新的见解。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Pathological observations show that cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration. However, general principles governing collective cell migration remain to be discovered. Different from individual cell migration, we demonstrated that the Notch-1-activation reduced collective cells speed and distances. In particular, Notch-1-activation induced cellular cytoskeletal remodelling, strengthened the intercellular junctions and cell-matrix adhesions. Mechanistically, Notch-1 activation prevented the phosphorylation of GSK-3β and the translocation of cytoplasmic free β-catenin to the nucleus, which increased E-cadherin expression and tight intercellular junctions. Moreover, Notch-1 signalling also activated the RhoA/ROCK pathway, promoting reorganization of F-actin and contractile forces produced by myosin. Further, Notch-1 activation increased cell adhesion to the extracellular substrate, which inhibited collective cell migration. These findings highlight that cell adhesions and cell-cell junctions contribute to collective cell migration and provide new insights into mechanisms of the modulation of Notch-1 signalling pathway on cancer cell malignancy.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.