集体细胞迁移（CCM）涉及多种生物过程，包括胚胎形态发生、血管生成和癌症侵袭。然而，CCM 的分子机制，尤其是前导细胞的形成，人们却知之甚少。在这里，我们利用哺乳动物上皮细胞和小鼠模型证明了调节血管动蛋白 (AMOT) 裂解的信号通路在 CCM 中发挥作用。在汇合的上皮单层中，全长 AMOT 位于细胞-细胞连接处并限制细胞运动。裂解后，AMOT（AMOT-CT）的C端片段易位至细胞-基质界面，促进粘着斑（FA）成熟，产生牵引力，诱导前导细胞形成。同时，细胞-细胞连接处全长 AMOT 的减少导致组织流化和细胞集体的连贯迁移。因此，AMOT 的裂解充当分子开关，产生极化收缩，促进前导细胞形成和 CCM。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Collective cell migration (CCM) is involved in multiple biological processes, including embryonic morphogenesis, angiogenesis, and cancer invasion. However, the molecular mechanisms underlying CCM, especially leader cell formation, are poorly understood. Here, we show that a signaling pathway regulating angiomotin (AMOT) cleavage plays a role in CCM, using mammalian epithelial cells and mouse models. In a confluent epithelial monolayer, full-length AMOT localizes at cell-cell junctions and limits cell motility. After cleavage, the C-terminal fragment of AMOT (AMOT-CT) translocates to the cell-matrix interface to promote the maturation of focal adhesions (FAs), generate traction force, and induce leader cell formation. Meanwhile, decreased full-length AMOT at cell-cell junctions leads to tissue fluidization and coherent migration of cell collectives. Hence, the cleavage of AMOT serves as a molecular switch to generate polarized contraction, promoting leader cell formation and CCM.Copyright © 2024 Elsevier Inc. All rights reserved.