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

Authors :
Yusuke Mori
Naoka Shiratsuchi
Nanami Sato
Azusa Chaya
Nobuyuki Tanimura
Susumu Ishikawa
Mugihiko Kato
Ikumi Kameda
Shunsuke Kon
Yukinari Haraoka
Tohru Ishitani
Yasuyuki Fujita
Source :
Current Biology. 32(10):2144-2159
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

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 extracellular 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.

Details

Language :
English
ISSN :
09609822
Volume :
32
Issue :
10
Database :
OpenAIRE
Journal :
Current Biology
Accession number :
edsair.doi.dedup.....cd6a9e0ab3929385e80d789cbcc63977