title: Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells.
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.
authors.affiliation: Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 302-718, Korea.
authors.forename: Kang Jin
authors.initials: KJ
authors.lastname: Jeong
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Seo
authors.forename: Kyung Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Jeung Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Jae Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology; D019061:src-Family Kinases
chemical_list: C412373:AG 1879; D002070:Butadienes; D005419:Flavonoids; D008246:Lysophospholipids; D009570:Nitriles; C545644:PTGER2 protein, human; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D011799:Quinazolines; D049368:Receptors, Lysophosphatidic Acid; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D020032:Tyrphostins; C113580:U 0126; C101044:RTKI cpd; D051546:Cyclooxygenase 2; D037342:Pertussis Toxin; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C032881:lysophosphatidic acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one