Abstract
Ovarian cancer is the fourth leading cause of cancer death among women in the United States. One of the biomarkers of ovarian cancer is lysophosphatidic acid (LPA). LPA is a type of G protein‐coupled receptor ligand. It is strikingly elevated in 90% of ovarian cancer patients. Additionally, LPA receptors are aberrantly up‐regulated in ovarian cancer patients. We have reported previously that a signaling axis consisting of beta‐arrestin 2 and CARMA3 (CARD and MAGUK domain‐containing protein 3) is indispensable in LPA‐induced nuclear factor kappa B (NF‐kappaB) activation in mouse embryonic fibroblast cells. NF‐kappaB is an important transcription factor, which has been suggested to mediate LPA‐induced ovarian cancer migration and invasion. However, it remains unknown whether the beta‐arrestin2‐CARMA3 signaling axis plays an important role in LPA‐induced ovarian cancer cell migration and invasion. In the present study, using beta‐arrestin 2 and CARMA3 shRNA, we knockdowned their protein expression levels in ovarian cancer cell lines. Consistent with previous reports, we found that down‐regulation of beta‐arrestin 2 and CARMA3 abolished LPA‐induced IKK activity and NF‐kappaB activation in ovarian cancer cells. In addition, in vitro transwell migration and matrigel invasion assays demonstrated that beta‐arrestin 2 and CARMA3 shRNA significantly impaired LPA‐induced ovarian cancer cell motility and invasiveness. Together, our results provide the evidence that β‐arrestin 2 and CARMA3 serve as critical regulators in LPA‐induced, NF‐kappaB‐mediated ovarian cancer migration and invasion. Therefore, we speculate that β‐arrestin 2 and CARMA3 may represent attractive therapeutic targets for ovarian cancer and many other types of malignancies.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B41.