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In a previous study, we demonstrated that high concentrations of Prostaglandin E2 (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ), which were expressed in tumor microenvironments, inhibited DCs\u2019 migration. However, the specific mechanism is not yet clear. The current study aims to use the murine bone marrow\u2013derived DCs (BMDCs) to demonstrate the possible signaling pathway of PGE\n                    <jats:sub>2<\/jats:sub>\n                    . The mRNA and protein expressions of the Epac1\u2013Rap1 axis and PKA\u2013CREB axis were determined after administration of PGE\n                    <jats:sub>2<\/jats:sub>\n                    on DCs. Then, the agonist and antagonist of these molecules were used to treat DCs. The migration capability of DCs was detected as well as the RhoA activation levels. The mRNA and protein of Epac1 were barely undetectable in DCs. The use of Epac1 agonists showed no impact on DCs\u2019 migration capability and RhoA activation levels. The activation levels of Rap1 and protein expressions of Rap1a and Rap1b were not affected by PGE\n                    <jats:sub>2<\/jats:sub>\n                    administration. The using of Rap1a and Rap1b antagonists demonstrated no impact on DCs\u2019 migration capability and RhoA activation levels. Moreover, the PKA activation levels and phosphorylated CREB1 were increased by the administration of PGE\n                    <jats:sub>2<\/jats:sub>\n                    on DCs. The application of a PKA inhibitor attenuated the effect of PGE\n                    <jats:sub>2<\/jats:sub>\n                    in a 3D migration assay and in vivo experiment. These results suggest that the PKA\u2013CREB axis, instead of Epac1\u2013Rap1, probably associates with the intracellular signaling pathway induced by high PGE\n                    <jats:sub>2<\/jats:sub>\n                    levels, which demonstrates an inhibitory effect on DCs\u2019 migration. These findings can bring a different perspective on immunological surveillance of tumor progression.\n                  <\/jats:p>","DOI":"10.1155\/sci5\/8715442","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:27:46Z","timestamp":1778758066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High PGE\n                    <sub>2<\/sub>\n                    Levels Inhibit the Migration of Dendritic Cells by Modulating the PKA\u2013CREB Axis Instead of 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