Angiomotin cleavage promotes leader formation and collective cell migration

Yu Wang; Yebin Wang; Yuwen Zhu; Pengcheng Yu; Fanhui Zhou; Anlan Zhang; Yuan Gu; Ruxin Jin; Jin Li; Fengyun Zheng; Aijuan Yu; Dan Ye; Yanhui Xu; Yan-Jun Liu; Thuan Beng Saw; Guohong Hu; Chwee Teck Lim; Fa-Xing Yu

doi:10.1016/j.devcel.2024.09.013

Angiomotin cleavage promotes leader formation and collective cell migration

Dev Cell. 2024 Oct 4:S1534-5807(24)00541-0. doi: 10.1016/j.devcel.2024.09.013. Online ahead of print.

Authors

Yu Wang¹, Yebin Wang¹, Yuwen Zhu¹, Pengcheng Yu¹, Fanhui Zhou¹, Anlan Zhang¹, Yuan Gu¹, Ruxin Jin¹, Jin Li¹, Fengyun Zheng¹, Aijuan Yu¹, Dan Ye², Yanhui Xu², Yan-Jun Liu², Thuan Beng Saw³, Guohong Hu⁴, Chwee Teck Lim⁵, Fa-Xing Yu⁶

Affiliations

¹ Institute of Pediatrics, Children's Hospital of Fudan University and The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
² Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
³ Research Center for Industries of the Future and School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China; Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
⁴ Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
⁵ Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore 117599, Singapore.
⁶ Institute of Pediatrics, Children's Hospital of Fudan University and The Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, The State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: fxyu@fudan.edu.cn.

PMID: 39389053
DOI: 10.1016/j.devcel.2024.09.013

Abstract

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.

Keywords: DDI2; Hippo; NF2; angiomotin; cleavage; collective cell migration; focal adhesion; leader cell; metastasis.