Collective cell migration is essential in various physiological processes, including embryonic development, wound healing, and cancer metastasis. However, the mechanisms by which individual cells achieve coordinated movement remain elusive. Here, we demonstrate that zonula occludens-1 (ZO-1), a scaffolding protein of tight junctions (TJs), dynamically translocates to form cell–extracellular matrix (ECM) adhesion complexes, podosomes, at the basal cell surface during migration. Extracellular signal-regulated kinase (ERK) activation triggers the translocation of ZO-1 to podosomes, where ZO-1 promotes invasive migration. ZO-1 also contributes to ERK activation dynamics within the cell collective, thereby influencing collective migratory behavior. In this work, we elucidate the dual roles of ZO-1 in coordinating intercellular signaling and invasive movement, providing insights into the mechanisms that integrate individual cell behaviors into a cohesive collective migration.
See details in Hirano et al., bioRxiv, 2024
Sayuki Hirano, Yohei Kondo, Asayuki Kitajima, Noriyuki Kinoshita, Tetsuhisa Otani, Mikio Furuse, Naoto Ueno, Kazuhiro Aoki (2026) ZO-1 shuttles between apical junctional complexes and podosomes by riding ERK activation waves., Nature communications
Published in May 9, 2026 (Electronic publication in May 9, 2026, midnight )
(Abstract) Collective cell migration is essential in various physiological processes, including embryonic development, wound healing, and cancer metastasis. However, the mechanisms by which individual cells achieve coordinated movement remain elusive. Here, we demonstrate that zonula occludens-1 (ZO-1), a scaffolding protein of tight junctions (TJs), dynamically translocates to form cell-extracellular matrix (ECM) adhesion complexes, podosomes, at the basal cell surface during migration. Extracellular signal-regulated kinase (ERK) activation triggers the translocation of ZO-1 to podosomes, where ZO-1 promotes invasive migration. ZO-1 also contributes to ERK activation dynamics within the cell collective, thereby influencing collective migratory behavior. In this work, we elucidate the dual roles of ZO-1 in coordinating intercellular signaling and invasive movement, providing insights into the mechanisms that integrate individual cell behaviors into a cohesive collective migration.