title: Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells.
abstract: Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca(2+) ([Ca(2+)]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca(2+) increase in these cells. In the present study, we further investigated actions of LPE not only in the [Ca(2+)]i increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of LPA1, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced Ca(2+) response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced Ca(2+) response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting LPA1 involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced Ca(2+) response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not LPA1) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized LPA1, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Kyoung-Pil
authors.initials: KP
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
keywords: Breast; GPCR; LPA1; Lysophosphatidic acid; Lysophosphatidylethanolamine; Receptor
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