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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, Jeong RakJang, Jin HyukOh, Seo JinKim, Min HyeShin, Chang HunJeong, Min SeokHeo, K.Park, J.Kim, S.R.Oh, Yong Seok
DGIST Authors
Jang, Jin Hyuk; Oh, Yong Seok
Issue Date
Cellular Signalling, 44, 138-147
Article Type
ezrinlysophosphatidic acidlysophosphatidic acid 1lysophosphatidic acid 2lysophosphatidic acid receptormoesinradixinRho guanine nucleotide binding proteinunclassified drugArticlecarboxy terminal sequencecell activationcell migrationcell mutantcontrolled studycytoskeletongene silencingLPA1 geneLPA2 genemembrane formationovarian cancer cell linepriority journalprotein expressionprotein phosphorylationsignal transduction
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
  • Author Oh, Yong Seok Laboratory of Neural Signaling Networks
  • Research Interests 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 SciencesLaboratory of Neural Signaling Networks1. Journal Articles

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