Dynamic Leader–Follower Hierarchies in Collective Cell Migration

Abstract

Collective migration of cancer cells, characterized by a structured leader–follower hierarchy, has emerged as a critical mechanism driving metastasis. During this process, leader cells play a pivotal role in environmental sensing, pathfinding, and signal transduction, while follower cells actively respond to these signals, facilitating stress transmission through cytoskeletal dynamics and cell–cell adhesions. Together, these interactions promote coordinated cancer invasion and metastasis. This review synthesizes current knowledge on the molecular mechanisms underlying leader–follower dynamics, with a particular emphasis on the role switching between them and the interplay of key signaling pathways. Building on recent studies, we explore how leader–follower plasticity influences collective behaviors and discuss its implications for cancer progression. By elucidating these mechanisms, we aim to identify potential therapeutic targets and propose novel strategies for disrupting collective invasion, offering new perspectives for cancer treatment.