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Journal of Cancer Research and Clinical Oncology

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Open Access 01-09-2020 | Sulprostone | Original Article – Cancer Research

Prostaglandin E2 receptor 3 (EP3) signaling promotes migration of cervical cancer via urokinase-type plasminogen activator receptor (uPAR)

Authors: Yao Ye, Lin Peng, Aurelia Vattai, Eileen Deuster, Christina Kuhn, Christian Dannecker, Sven Mahner, Udo Jeschke, Viktoria von Schönfeldt, Helene H. Heidegger

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2020

Abstract

Purpose

Cervical cancer metastasis results in poor prognosis and increased mortality, which is not separated from inflammatory reactions accumulated by prostaglandin E2 (PGE2). As a specific G-protein coupled PGE2 receptor, EP3 is demonstrated as a negative prognosticator of cervical malignancy. Now, we aimed to investigate the pathological mechanism of EP3 in modulating cervical cancer carcinogenesis.

Methods

Bioinformatics analysis was used to identify PAI-1 and uPAR correlations with EP3 expression, as well as the prognosis of cervical cancer patients. In vitro analyses were carried out to investigate the role of EP3 on cervical cancer proliferation and migration.

Results

In vitro studies showed that sulprostone (an EP3 agonist) enhanced the proliferation and migration of cervical cancer cells, whereas silencing of EP3 inhibited their proliferation and migration. Furthermore, EP3 knockdown increased the expression of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator receptor (uPAR), and phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2), but decreased p53 expression. Bioinformatics analysis showed that both PAI-1 and uPAR were correlated with EP3 expression, as well as the prognosis of cervical cancer patients. The survival analysis further showed that uPAR overexpression (IRS≥2) was correlated with a lower overall survival rate of cervical cancer patients with advanced stages (FIGO III-IV).

Conclusion

These results indicated that EP3 signaling pathway might facilitate the migration of cervical cancer cells through modulating uPAR expression. Therefore, EP3 and uPAR could represent novel therapeutic targets in the treatment of cervical cancer in advantaged stages.

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Title: Prostaglandin E2 receptor 3 (EP3) signaling promotes migration of cervical cancer via urokinase-type plasminogen activator receptor (uPAR)
Authors: Yao Ye
Lin Peng
Aurelia Vattai
Eileen Deuster
Christina Kuhn
Christian Dannecker
Sven Mahner
Udo Jeschke
Viktoria von Schönfeldt
Helene H. Heidegger
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Sulprostone
Cervical Cancer
Urokinase
Cervical Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03272-0

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Purpose

Methods

Results

Conclusion

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