Back to Search
Start Over
Transactivation of epidermal growth factor receptor through platelet-activating factor/receptor in ovarian cancer cells
- Source :
- Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Background We 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. Methods Expression 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. Results Our 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. Conclusions The 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.
- Subjects :
- Transcriptional Activation
MAPK/ERK pathway
Cancer Research
medicine.medical_specialty
endocrine system diseases
Platelet Membrane Glycoproteins
Models, Biological
Receptors, G-Protein-Coupled
Transactivation
Cell Line, Tumor
Internal medicine
Humans
Medicine
Growth factor receptor inhibitor
Epidermal growth factor receptor
Phosphorylation
Platelet Activating Factor
Ovarian cancer cells
Protein Kinase C
Platelet-activating factor receptor
Mitogen-Activated Protein Kinase 1
Ovarian Neoplasms
Mitogen-Activated Protein Kinase 3
biology
business.industry
Research
medicine.disease
female genital diseases and pregnancy complications
ErbB Receptors
Gene Expression Regulation, Neoplastic
src-Family Kinases
Endocrinology
Oncology
Metalloproteases
Cancer research
biology.protein
Calcium
Female
Signal transduction
business
Ovarian cancer
Tyrosine kinase
Signal Transduction
Subjects
Details
- ISSN :
- 17569966
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....b1633755903e0e32dae79639dad29fea