Dynamic forces shape the survival fate of eliminated cells

Abstract

Tissues eliminate unfit, unwanted or unnecessary cells through cell extrusion, and this can lead to the elimination of both apoptotic and live cells. However, the mechanical signatures that influence the fate of extruding cells remain unknown. Here we show that modified force transmission across adherens junctions inhibits apoptotic cell eliminations. By combining cell experiments with varying levels of E-cadherin junctions and three-dimensional modelling of cell monolayers, we find that these changes not only affect the fate of the extruded cells but also shift extrusion from the apical to the basal side, leading to cell invasion into soft collagen gels. We generalize our findings using xenografts and cysts cultured in matrigel, derived from patients with breast cancer. Our results link intercellular force transmission regulated by cell–cell communication to cell extrusion mechanisms, with potential implications during morphogenesis and invasion of cancer cells.