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Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells

Authors
 Kang Jin Jeong  ;  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 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.40(6) : 607-616, 2008 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2008
Keywords
cell movement ; cyclooxygenase-2 ; lysophosphatidic acid ; ovarian neoplasms ; proto-oncogene proteins pp60 (c-src) ; receptors ; lysophosphatidic acid
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
Files in This Item:
T2008L0002.pdf Download
DOI
10.3858/emm.2008.40.6.607
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Lee, Hoi Young(이효영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108692
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