2020年3月
Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.
Genes to cells : devoted to molecular & cellular mechanisms
- 巻
- 25
- 号
- 3
- 開始ページ
- 197
- 終了ページ
- 214
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/gtc.12750
- 出版者・発行元
- Wiley
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.
- リンク情報
- ID情報
-
- DOI : 10.1111/gtc.12750
- ISSN : 1356-9597
- eISSN : 1365-2443
- PubMed ID : 31989743
- PubMed Central 記事ID : PMC7078805