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 language | English (US) |
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Pages (from-to) | 3771-3780 |
Number of pages | 10 |
Journal | FEBS Letters |
Volume | 591 |
Issue number | 22 |
DOIs | |
State | Published - 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