Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extra cellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an ???extrude me???signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.

Automated summary

This study found that reactive oxygen species (ROS) are elevated in the surrounding epithelial layers during cell extrusion, and reducing ROS levels inhibits the extrusion process. Additionally, extruding cells release ATP, which promotes ROS levels and cell extrusion. The extracellular ATP and ROS pathways also regulate the movement of surrounding cells towards the extruding cells. These findings highlight the important role of extracellular ATP in cell extrusion.