Mammary Epithelial Migration is EMT-Independent

ABSTRACT Epithelial tissues are traditionally considered immobile, requiring epithelial-to-mesenchymal transition (EMT) for individual or collective cell migration as mesenchymal cells. However, recent studies indicate that the mammary epithelium migrates via mechanisms distinct from mesenchymal collectives. Here, we demonstrate that mammary epithelium does not undergo EMT before migration, as evidenced by cellular and molecular characteristics, including EMT marker expression at the mRNA, protein, localization, and transcriptomic levels. Contrary to established models, cell-cell adhesion is not diminished but is required for epithelial migration. Furthermore, Snail1 does not repress cell-cell adhesion but instead plays a pivotal role in directing epithelial migration by regulating processes such as the directional movement of individual cells via Cdc42ep5 . Our findings reveal the existence of both stationary and migratory states within the epithelium, providing new insights into how epithelial tissues transition between these states, with broad implications for organogenesis and cancer biology.