Regulation of intercellular viscosity by E-cadherin-dependent phosphorylation of EGFR in collective cell migration

• 成果类型: Article
• 署名作者: Fu, Chaoyu; Dilasser, Florian; Lin, Shao-Zhen; Karnat, Marc; Arora, Aditya; Rajendiran, Harini; Ong, Hui Ting; Brenda, Nai Mui Hoon; Phow, Sound Wai; Hirashima, Tsuyoshi; Sheetz, Michael; Rupprecht, Jean-Francois; Tlili, Sham; Viasnoff, Virgile
• 署名单位: National University of Singapore; Aix-Marseille Universite; Universite de Toulon; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); National University of Singapore; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15126
• DOI: 10.1073/pnas.2405560121
• 发表日期: 2024-09-10
• 关键词: tension; rhoa; contraction; activation; DYNAMICS; forces

摘要

Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role in regulating cell cohesion and migration dynamics during tissue remodeling. While the role and origin of the junctional mechanical tension at AJs have been extensively studied, the influence of the actin cortex structure and dynamics on junction plasticity remains incompletely understood. Moreover, the mechanisms underlying stress dissipation at junctions are not well elucidated. Here, we found that the ligandindependent phosphorylation of epithelial growth factor receptor (EGFR) downstream of de novo E-cadherin adhesion orchestrates a feedback loop, governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. This modulation of effective viscosity coordinates cellular movements within the expanding monolayer, inducing a transition from swirling to laminar flow patterns while maintaining a constant migration front speed. Additionally, we propose a vertex model with adjustable junctional viscosity, capable of replicating all observed cellular flow phenotypes experimentally.