Exp Mol Med.
2008 Dec;40(6):607-616. 10.3858/emm.2008.40.6.607.
Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells
- Affiliations
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- 1Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Korea. hoi@konyang.ac.kr
- 2Department of Immunology and Physiology, College of Medicine, Konkuk University, Chungju, Korea.
- 3Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, Suwon, Korea.
- 4Department of Pharmacology, College of Medicine, Kwandong University, Gangneung, Korea .
- KMID: 1072941
- DOI: http://doi.org/10.3858/emm.2008.40.6.607
Abstract
- Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.
Keyword
MeSH Terms
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Butadienes/pharmacology
Cell Line, Tumor
Cell Movement/drug effects/*physiology
Cyclooxygenase 2/*biosynthesis
Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism
Female
Flavonoids/pharmacology
GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors/*metabolism
Humans
Lysophospholipids/pharmacology
Nitriles/pharmacology
Ovarian Neoplasms/metabolism/*pathology
Pertussis Toxin/pharmacology
Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism
Proto-Oncogene Proteins/antagonists & inhibitors/*metabolism
Pyrimidines/pharmacology
Receptor, Epidermal Growth Factor/antagonists & inhibitors/metabolism
Receptors, Lysophosphatidic Acid/*metabolism
Receptors, Prostaglandin E/metabolism
Signal Transduction
Transcriptional Activation
Tyrphostins/pharmacology
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