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  • Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.

Genes to cells : devoted to molecular & cellular mechanisms (2020-01-29)
Erika Ishihara, Yuya Nagaoka, Toshiaki Okuno, Satoshi Kofuji, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Kenya Kamimura, Shuji Terai, Takehiko Yokomizo, Yukihiko Sugimoto, Yasuyuki Fujita, Akira Suzuki, Hiroshi Nishina
ABSTRACT

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 PGE2 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 PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)