Mechanisms Underlying the Initiation and Termination of Collective Cell Migration: Perspectives for Understanding Development and Cancer Metastasis

Abstract

Collective cell migration is fundamental to developmental processes and disease progression. Despite extensive study, the field lacks a unifying framework for how collective cells initiate and terminate their migration. While these processes have traditionally been explained for individual cell migration by epithelial‒mesenchymal transition (EMT) and mesenchymal‒epithelial transition (MET), these models do not fully recapitulate the complex features of collective cell migration. In this review, I explore the distinct mechanisms by which groups of cells initiate and terminate collective migration, highlighting in vivo examples such as gastrulation and neural crest formation in vertebrates, lateral line migration in zebrafish, and tracheal branch and border cell migration in Drosophila. I also discuss collective cell migration in cancer metastasis. I focus on how the initiation and termination of collective migration are regulated, emphasizing the regulatory pathways and unique features. Clarifying these mechanisms will guide hypothesis-driven discovery and inform strategies to modulate collective cell behaviors in development, regeneration, and metastasis.