期刊
CELL REPORTS
卷 40, 期 2, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.111078
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资金
- Japan Society for the Promotion of Science (JSPS) [21H05285A01, 21H05039, 20K21411, 21H05291, 21H05287, JP20J20930, JP21J01076, 19H03412]
- JSPS Bilateral Joint Research Projects (The Royal Society) [JPJSBP1 20215703]
- Japan Science and Technology Agency (JST) (Moonshot RD) [JPMJPS2022]
- Takeda Science Foundation
- SAN-ESU GIKEN
- AMED PRIME program [20gm5810025h9904]
- AMED [JP20gm5010001]
- Kyoto University Live Imaging Center
In vertebrates, normal cells neighboring transformed cells can enhance cell competition and accelerate the apical extrusion of transformed cells through calcium sparks and phosphorylation of AHNAK2.
In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calciumsparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechano-sensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.
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