Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells.
10.3858/emm.2008.40.6.607
- Author:
Kang Jin JEONG
1
;
Soon Young PARK
;
Ji Hye SEO
;
Kyung Bok LEE
;
Wahn Soo CHOI
;
Jeung Whan HAN
;
Jae Ku KANG
;
Chang Gyo PARK
;
Yong Kee KIM
;
Hoi Young LEE
Author Information
1. Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Korea. hoi@konyang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell movement;
cyclooxygenase-2;
lysophosphatidic acid;
ovarian neoplasms;
proto-oncogene proteins pp60 (c-src);
receptors, lysophosphatidic acid
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(6):607-616
- CountryRepublic of Korea
- Language:English
-
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.
