ArticleBreast cancer research and treatment2014
Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties.
Article in Breast cancer research and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- Recent advances in targeting COX-2 for cancer therapy: a review.RSC medicinal chemistry · 2025Review
- Acquired resistance to jadomycin B in human triple-negative breast cancer cells is associated with increased cyclooxygenase-2 expression.The Journal of pharmacology and experimental therapeutics · 2025Article
- Pivotal roles for cancer cell-intrinsic mPGES-1 and autocrine EP4 signaling in suppressing antitumor immunity.JCI insight · 2024Article
- Sea Cucumber Derived Triterpenoid Glycoside Frondoside A: A Potential Anti-Bladder Cancer Drug.Nutrients · 2023Article
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- Investigation of the Role of PUFA Metabolism in Breast Cancer Using a Rank-Based Random Forest Algorithm.Cancers · 2022Article
- Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy.Cancer research · 2022Review
- NFκB-Activated COX2/PGECancers · 2021Article
- Review
- Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/AKT axis regulation.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Clinical and Biological Implications of Cancer Stem Cells in Hepatocellular Carcinoma.Yonago acta medica · 2021Review
- The Prostaglandin E2 Pathway and Breast Cancer Stem Cells: Evidence of Increased Signaling and Potential Targeting.Frontiers in oncology · 2021Review
- Editorial: Eicosanoids in Cancer.Frontiers in pharmacology · 2021Article
- An Extract of Taro (Breast cancer : basic and clinical research · 2021Article
- Article
- EP3 Is an Independent Prognostic Marker Only for Unifocal Breast Cancer Cases.International journal of molecular sciences · 2020Article
- Monocarboxylate Transporter 6-Mediated Interactions with Prostaglandin FPharmaceutics · 2020Article
- Eicosanoids in Cancer: Prostaglandin EFrontiers in pharmacology · 2020Review
- EP4 and Class III β-Tubulin Expression in Uterine Smooth Muscle Tumors: Implications for Prognosis and Treatment.Cancers · 2019Article
- The Chemokine Receptor CXCR3 Isoform B Drives Breast Cancer Stem Cells.Breast cancer : basic and clinical research · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The cyclooxygenase pathway is strongly implicated in breast cancer progression but the role of this pathway in the biology of breast cancer stem/progenitor cells has not been defined. Recent attention has focused on targeting the cyclooxygenase 2 (COX-2) pathway downstream of the COX-2 enzyme by blocking the activities of individual prostaglandin E (EP) receptors. Prostaglandin E receptor 4 (EP4) is widely expressed in primary invasive ductal carcinomas of the breast and antagonizing this receptor with small molecule inhibitors or shRNA directed to EP4 inhibits metastatic potential in both syngeneic and xenograft models. Breast cancer stem/progenitor cells are defined as a subpopulation of cells that drive tumor growth, metastasis, treatment resistance, and relapse. Mammosphere-forming breast cancer cells of human (MDA-MB-231, SKBR3) or murine (66.1, 410.4) origin of basal-type, Her-2 phenotype and/or with heightened metastatic capacity upregulate expression of both EP4 and COX-2 and are more tumorigenic compared to the bulk population. In contrast, luminal-type or non-metastatic counterparts (MCF7, 410, 67) do not increase COX-2 and EP4 expression in mammosphere culture. Treatment of mammosphere-forming cells with EP4 inhibitors (RQ-15986, AH23848, Frondoside A) or EP4 gene silencing, but not with a COX inhibitor (Indomethacin) reduces both mammosphere-forming capacity and the expression of phenotypic markers (CD44(hi)/CD24(low), aldehyde dehydrogenase) of breast cancer stem cells. Finally, an orally delivered EP4 antagonist (RQ-08) reduces the tumor-initiating capacity and markedly inhibits both the size of tumors arising from transplantation of mammosphere-forming cells and phenotypic markers of stem cells in vivo. These studies support the continued investigation of EP4 as a potential therapeutic target and provide new insight regarding the role of EP4 in supporting a breast cancer stem cell/tumor-initiating phenotype.
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