Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.
Genes Cells
; 25(3): 197-214, 2020 Mar.
Article
in En
| MEDLINE
| ID: mdl-31989743
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Dinoprostone
/
Signal Transduction
/
Cell Cycle Proteins
/
Receptors, Prostaglandin E, EP2 Subtype
/
Cell Competition
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Genes Cells
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Document type:
Article
Affiliation country:
Japan