ArticleJournal of experimental & clinical cancer research : CR2014
Transactivation of epidermal growth factor receptor through platelet-activating factor/receptor in ovarian cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Impact of the crosstalk between the PTEN and PAFR as well as PAFR and EGFR pathways in cancer.Exploration of drug science · 2025Article
- The Multiple Functions of HB-EGF in Female Reproduction and Related Cancer: Molecular Mechanisms and Targeting Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.Molecules (Basel, Switzerland) · 2023Review
- Review
- Platelet-activating factor acetyl hydrolase IB2 dysregulated cell proliferation in ovarian cancer.Cancer cell international · 2021Article
- Article
- Platelet-Activating Factor-Receptor Signaling Mediates Targeted Therapies-Induced Microvesicle Particles Release in Lung Cancer Cells.International journal of molecular sciences · 2020Article
- Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease.Journal of lipid research · 2020Review
- Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer.Frontiers in oncology · 2020Article
- TNFα promotes mucosal wound repair through enhanced platelet activating factor receptor signaling in the epithelium.Mucosal immunology · 2019Article
- Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy.Clinics (Sao Paulo, Brazil) · 2018Review
- Inflammation, not Cholesterol, Is a Cause of Chronic Disease.Nutrients · 2018Review
- PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells.Oncotarget · 2017Article
- Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research.International journal of molecular sciences · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously identified platelet-activating factor receptor (PAFR) as being overexpressed in ovarian cancer and found that its ligand PAF evoked EGFR phosphorylation using the phospho-antibody microarray. Epidermal growth factor receptor (EGFR) are also overexpressed in ovarian cancer and contribute to the growth of ovarian cancer cells. Here, we investigated the mechanisms of crosstalk between PAFR and EGFR signaling in ovarian cancer cells to further determine whether the interaction between PAFR and EGFR synergistic contribute to the progression of ovarian cancer.
methodsExpression and localization of PAFR in several ovarian cancer cell lines were assessed by Western blot, realtime-PCR and immunofluorescence. The ovarian cancer cells were stimulated with PAF or PAF and in some experiments also pharmacological inhibitors. Phosphorylation of proteins in signaling pathways were measured by Western blot. HB-EGF concentrations of the supernatant from stimulated ovarian cancer cells were measured by enzyme-linked immunosorbent assay.
resultsOur data show that PAF increases EGFR phosphorylation through PAFR in a time- and dose- dependent manner in SKOV-3 ovarian cancer cells. This transactivation is dependent on phospholipase C-β and intracellular calcium signaling. This pathway is also Src tyrosine kinase- and metalloproteinase- dependent. PAF triggers EGFR activation through the increased heparin-binding EGF-like growth factor (HB-EGF) release in metalloprotease-dependent manner. Several studies involving EGFR transactivation through G-protein coupled receptor (GPCR) have demonstrated EGFR-dependent increase in ERK1/2 phosphorylation. Yet in SKOV-3 cells, PAF treatment also increases ERK1/2 phosphorylation in a EGFR-independent manner.
conclusionsThe results suggest that in SKOV-3 ovarian cancer cells, PAF transactivates EGFR and downstream ERK pathways, thus diversifying the GPCR-mediated signal. The crosstalk between PAFR and EGFR suggests a potentially important signaling linkage between inflammatory and growth factor signaling in ovarian cancer cells.
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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 Socratic graph.