PGE1 and E3 show lower efficacies than E2 to β-catenin-mediated activity as biased ligands of EP4 prostanoid receptors

Yumi Araki, Akiko Suganami, Suzu Endo, Yuta Masuda, Keijo Fukushima, John W. Regan, Toshihiko Murayama, Yutaka Tamura, Hiromichi Fujino

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The 2-series of prostaglandin E (PGE2) is regarded as a pro-cancer prostanoid, whereas the 1-series (PGE1) and the 3-series (PGE3) are considered to act as anti-cancer prostanoids. In the present study, we provide possible reasons why PGE1 and PGE3, but not PGE2, exert anti-cancer effects by focusing on each diverged E-type prostanoid (EP)4 receptor-mediated signaling pathway. PGE1, PGE2 and PGE3 function as full agonists in terms of Gαs- and Gαi-protein-mediated signaling. However, PGE1 and PGE3 function as partial agonists of T-cell factor (TCF)/β-catenin (β-cat)-mediated activity, the well-known cancer-related signaling pathway. Furthermore, pretreatment with PGE1 or PGE3 almost completely reduces PGE2-induced TCF/β-cat activity. These results provide a plausible reason why PGE1 and PGE3 function as anti-cancer prostanoids as a result of novel biased activity for EP4 receptors.

Original languageEnglish (US)
Pages (from-to)3771-3780
Number of pages10
JournalFEBS Letters
Volume591
Issue number22
DOIs
StatePublished - Nov 2017

Keywords

  • E-type prostanoid 4 receptors
  • PGE
  • PGE
  • PGE
  • TCF/β-catenin signaling
  • biased ligands

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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