2. Academic Validation
  3. 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 Cells. 2020 Mar;25(3):197-214. doi: 10.1111/gtc.12750.
Erika Ishihara 1,  Yuya Nagaoka 1,  Toshiaki Okuno 2,  Satoshi Kofuji 1,  Mari Ishigami-Yuasa 3,  Hiroyuki Kagechika 3,  Kenya Kamimura 4,  Shuji Terai 4,  Takehiko Yokomizo 2,  Yukihiko Sugimoto 5,  Yasuyuki Fujita 6,  Akira Suzuki 7,  Hiroshi Nishina 1
Affiliations

Affiliations

  • 1 Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • 2 Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 3 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • 4 Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
  • 5 Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • 6 Division of Molecular Oncology, Institute for Genetic Medicine, Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Japan.
  • 7 Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
PMID: 31989743 DOI: 10.1111/gtc.12750
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.

Keywords

COX-2; E-cadherin internalization; PGE2; YAP; cell competition.

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