Calcium Wave Promotes Cell Extrusion.

When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis. However, the underlying molecular mechanism still remains elusive. In this study, we first show, using mammalian cultured epithelial cells and zebrafish embryos, that prior to apical extrusion of RasV12-transformed cells, calcium wave occurs from the transformed cell and propagates across the surrounding cells. The calcium wave then triggers and facilitates the process of extrusion. IP 3 receptor, gap junction, and mechanosensitive calcium channel TRPC1 are involved in calcium wave. Calcium wave induces the polarized movement of the surrounding cells toward the extruding transformed cells. Furthermore, calcium wave facilitates apical extrusion, at least partly, by inducing actin rearrangement in the surrounding cells. Moreover, comparable calcium propagation also promotes apical extrusion of apoptotic cells. Thus, calcium wave is an evolutionarily conserved, general regulatory mechanism of cell extrusion. • Calcium wave propagates from extruding cells within the epithelium • Calcium wave promotes apical extrusion of transformed or apoptotic cells • IP 3 R, gap junction, and TRPC1 are involved in calcium wave • Calcium wave induces polarized movement of surrounding cells toward extruding cells Takeuchi et al. demonstrate, using mammalian cell culture and zebrafish embryos, that calcium wave explosively propagates from extruding cells toward the surrounding cells within epithelia. Calcium wave promotes apical extrusion of transformed or apoptotic cells by inducing the polarized movement of the surrounding cells toward extruding cells. [ABSTRACT FROM AUTHOR]