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Review
. 2023 Apr 19;15(8):2374.
doi: 10.3390/cancers15082374.

Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

Federica Finetti  1 , Lucrezia Paradisi  1 , Clizia Bernardi  1 , Margherita Pannini  1 , Lorenza Trabalzini  1
Affiliations
Review

Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

Federica Finetti et al. Cancers (Basel). .

Abstract

It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and it is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune escape. In addition, the expression of the enzymes involved in PGE2 synthesis, cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES1), positively correlates with tumor progression and aggressiveness, clearly indicating the crucial role of the entire pathway in cancer. Moreover, several lines of evidence suggest that the COX2/mPGES1/PGE2 inflammatory axis is involved in the modulation of epidermal growth factor receptor (EGFR) signaling to reinforce the oncogenic drive of EGFR activation. Similarly, EGFR activation promotes the induction of COX2/mPGES1 expression and PGE2 production. In this review, we describe the interplay between COX2/mPGES1/PGE2 and EGFR in cancer, and new therapeutic strategies that target this signaling pathway, to outline the importance of the modulation of the inflammatory process in cancer fighting.

Keywords: COX2; EGFR; PGE2; TKRs; cancer; extrinsic inflammation; intrinsic inflammation; mPGES1; tumor angiogenesis; tumor progression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biosynthesis of prostaglandins. Arachidonic acid (AA) is a phospholipid present in cell membranes and is liberated from the cellular membranes by cytoplasmic phospholipase A2 (PLA2). Free AA is converted to PGE2 through the COX pathway. AA is metabolized to the intermediate prostaglandin G2 (PGG2), which is then reduced to PGH2 by the peroxidase activity of COX. PGH2 is sequentially metabolized to PGE2 or other eicosanoids by specific synthases.
Figure 2
Figure 2
Schematic representation of EP receptors. PGE2 activity is mediated by the interaction with four G-protein-coupled receptors (GPCRs), namely, EP1–EP4 receptors. Each EP receptor possesses a distinct signaling pathway.
Figure 3
Figure 3
Crosstalk between PGE2 and EGFR. PGE2 promotes EGFR phosphorylation and internalization through the activation of different signaling pathways. PGE2 promotes EGFR phosphorylation either by EP-mediated Src or PKA activation, or by inducing the release of EGFR ligands (MMPs activation). Similarly, IL-1β signaling promotes EGFR activation through the increased production of CXCL1, which in turn activates EGFR through CXCR2, or by a Src-mediated mechanism. AC = adenylate cyclase; PGE2 = prostaglandin E2; EP = prostaglandin E2 receptor; cAMP = cyclic adenosine monophosphate; PKA = protein kinase A; Src = SRC proto-oncogene; EGFR = epidermal growth factor receptor; nEGFR = nuclear EGFR; EGF = epidermal growth factor; PI3K = phosphatidylinositol 4,5-bisphosphate 3-kinase; p42/44 MAPK = p42/44 mitogen-activated protein kinases; TF = tissue factor; MMPs = matrix metalloproteinases; IL-1β = interleukin 1β; CXCR2 = CXC motif chemokine receptor 2; CXCL1 = C-X-C motif chemokine ligand 1; COX-2 = cyclooxygenase 2; mPGES1 = microsomal prostaglandin E synthase 1; iNOS = inducible nitric oxide synthase.
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References

    1. Mollaei M., Abbasi A., Hassan Z.M., Pakravan N. The Intrinsic and Extrinsic Elements Regulating Inflammation. Life Sci. 2020;260:118258. doi: 10.1016/j.lfs.2020.118258. - DOI - PubMed
    1. Porta C., Larghi P., Rimoldi M., Grazia Totaro M., Allavena P., Mantovani A., Sica A. Cellular and Molecular Pathways Linking Inflammation and Cancer. Immunobiology. 2009;214:761–777. doi: 10.1016/j.imbio.2009.06.014. - DOI - PubMed
    1. Mantovani A., Pierotti M.A. Cancer and Inflammation: A Complex Relationship. Cancer Lett. 2008;267:180–181. doi: 10.1016/j.canlet.2008.05.003. - DOI - PubMed
    1. Piotrowski I., Kulcenty K., Suchorska W. Interplay between Inflammation and Cancer. Rep. Pract. Oncol. Radiother. 2020;25:422–427. doi: 10.1016/j.rpor.2020.04.004. - DOI - PMC - PubMed
    1. Korniluk A., Koper O., Kemona H., Dymicka-Piekarska V. From Inflammation to Cancer. Ir. J. Med. Sci. 2017;186:57–62. doi: 10.1007/s11845-016-1464-0. - DOI - PMC - PubMed

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This research received no external funding.