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Department of Chemitry

International Journal

Cellular Signalling
년도 2018
학술지명 Cellular Signalling
논문명 LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2
게재권/집 vol.44/138-147
수록페이지
저자명 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
Link 관련링크 https://www.sciencedirect.com/science/article/pii/S0898656818300135?vi… 3931회 연결
Abstract
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.