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LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2
- LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2
- Park, Jeongrak; Jang, Jin-Hyeok; Oh, Seo Jin; Kim, Min Hye; Shin, Chang Hun; Jeong, Min Seok; Heo, Kyun; Park, Jong Bae; Kim, Sang Ryong; Oh, Yong Seok
- DGIST Authors
- Jang, Jin-Hyeok; Oh, Yong Seok
- Issue Date
- Cellular Signalling, 44, 138-147
- Article Type
- Author Keywords
- Cell migration; ERM (ezrin/radixin/moesin) proteins; LPA receptor; Lysophosphatidic acid (LPA); Ovarian cancer; RhoA
- Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian cancer. This phospholipid elicits a wide range of cancer cell responses, such as proliferation, trans-differentiation, migration, and invasion, via various G-protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling pathway via which LPA induces migration of ovarian cancer cells. LPA induced robust phosphorylation of ezrin/radixin/moesin (ERM) proteins, which are membrane-cytoskeleton linkers, in the ovarian cancer cell line OVCAR-3. Among the LPAR subtypes expressed in these cells, LPA1 and LPA2, but not LPA3, induced phosphorylation of ERM proteins at their C-termini. This phosphorylation was dependent on the Gα12/13/RhoA pathway, but not on the Gαq/Ca2+/PKC or Gαs/adenylate cyclase/PKA pathway. The activated ERM proteins mediated cytoskeletal reorganization and formation of membrane protrusions in OVCAR-3 cells. Importantly, LPA-induced migration of OVCAR-3 cells was completely abolished not only by gene silencing of LPA1 or LPA2, but also by overexpression of a dominant negative ezrin mutant (ezrin-T567A). Taken together, this study demonstrates that the LPA1/LPA2/ERM pathway mediates LPA-induced migration of ovarian cancer cells. These findings may provide a potential therapeutic target to prevent metastatic progression of ovarian cancer. © 2018 Elsevier Inc.
- Elsevier Inc.
- Related Researcher
Molecular Psychiatry Lab
Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
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Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles
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