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Prostaglandin E 2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition
Author(s) -
Ishihara Erika,
Nagaoka Yuya,
Okuno Toshiaki,
Kofuji Satoshi,
IshigamiYuasa Mari,
Kagechika Hiroyuki,
Kamimura Kenya,
Terai Shuji,
Yokomizo Takehiko,
Sugimoto Yukihiko,
Fujita Yasuyuki,
Suzuki Akira,
Nishina Hiroshi
Publication year - 2020
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12750
Subject(s) - adenylyl cyclase , biology , microbiology and biotechnology , internalization , signal transduction , prostaglandin e2 receptor , receptor , secretion , prostaglandin , prostaglandin e , cell , intracellular , cell signaling , biochemistry , agonist
Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE 2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE 2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.