ArticleOncotarget2017
PGE2/EP3/SRC signaling induces EGFR nuclear translocation and growth through EGFR ligands release in lung adenocarcinoma cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Effect of Concomitant Use of Analgesics on Prognosis in Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2022Pooled it
- Repurposing Niflumic Acid-Loaded PEGylated Cerosomes for Topical Solid Ehrlich's Carcinoma Management via EGFR/ERK/miR-21 Signaling Pathway Modulation.Pharmaceutics · 2026Article
- Wood smoke particles elicit events associated with adverse effects in human lung epithelial cells.Frontiers in toxicology · 2026Article
- The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Role of nitric oxide, prostaglandins, thromboxanes and endothelins in lung cancer: An overview.World journal of clinical cases · 2025Review
- Restoration of Osimertinib sensitivity in lung cancer through BRD4 inhibitor-mediated depalmitoylation of mutant EGFR via APT1.NPJ precision oncology · 2025Article
- Concomitant Use of Analgesics and EGFR TKIs in Lung Cancer Patients: Outcomes and Perspectives From a Finnish Retrospective Register-Based Study.Cancer medicine · 2025Article
- Celecoxib prevents malignant progression of smoking-induced lung tumors via suppression of the COX-2/PGEFrontiers in immunology · 2025Article
- Review
- Amphiregulin orchestrates the paracrine immune-suppressive function of amniotic-derived cells through its interplay with COX-2/PGEiScience · 2024Article
- WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways.American journal of physiology. Cell physiology · 2024Article
- Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy.Current issues in molecular biology · 2024Article
- Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy.Cancer research · 2022Review
- Inhibition of PKC/MEK pathway suppresses β1-integrin and mitigates breast cancer cells proliferation.Toxicology reports · 2021Article
- Review
- Targeting endothelial-to-mesenchymal transition: the protective role of hydroxytyrosol sulfate metabolite.European journal of nutrition · 2020Article
- Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer.Translational lung cancer research · 2020Review
- NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGECancers · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in both tumor and stromal cells supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2 promotes nuclear translocation of epidermal growth factor receptor (nEGFR), affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are required for the effect of PGE2 on nEGFR and downstream signaling activities. PGE2 binds its bona fide receptor EP3 which by activating SRC family kinases, induces ADAMs activation which, in turn, releases EGFR-ligands from the cell membrane and promotes nEGFR. Amphiregulin (AREG) and Epiregulin (EREG) appear to be involved in nEGFR promoted by the PGE2/EP3-SRC axis. Pharmacological inhibition or silencing of the PGE2/EP3/SRC-ADAMs signaling axis or EGFR ligands i.e. AREG and EREG expression abolishes nEGFR induced by PGE2. In conclusion, PGE2 induces NSCLC cell proliferation by EP3 receptor, SRC-ADAMs activation, EGFR ligands shedding and finally, phosphorylation and nEGFR. Since nuclear EGFR is a hallmark of cancer aggressiveness, our findings reveal a novel mechanism for the contribution of PGE2 to tumor progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.