title: Lysophosphatidylethanolamine utilizes LPA(1) and CD97 in MDA-MB-231 breast cancer cells.
abstract: Lysophosphatidylethanolamine (LPE) is a lyso-type metabolite of phosphatidylethanolamine (a plasma membrane component), and its intracellular Ca(2+) ([Ca(2+)]i) increasing actions may be mediated through G-protein-coupled receptor (GPCR). However, GPCRs for lysophosphatidic acid (LPA), a structurally similar representative lipid mediator, have not been implicated in LPE-mediated activities in SK-OV3 or OVCAR-3 ovarian cancer cells or in receptor over-expression systems. In the present study, LPE-induced [Ca(2+)]i increase was observed in MDA-MB-231 cells but not in other breast cancer cell lines. In addition, LPE- and LPA-induced responses showed homologous and heterologous desensitization. Furthermore, VPC32183 and Ki16425 (antagonists of LPA1 and LPA3) inhibited LPE-induced [Ca(2+)]i increases, and knockdown of LPA1 by transfection with LPA1 siRNA completely inhibited LPE-induced [Ca(2+)]i increases. Furthermore, the involvement of CD97 (an adhesion GPCR) in the action of LPA1 in MDA-MB-231 cells was demonstrated by siRNA transfection. Pertussis toxin (a specific inhibitor of Gi/o proteins), edelfosine (an inhibitor of phospholipase C), or 2-APB (an inhibitor of IP3 receptor) completely inhibited LPE-induced [Ca(2+)]i increases, whereas HA130, an inhibitor of autotaxin/lysophospholipase D, did not. Therefore, LPE is supposed to act on LPA1-CD97/Gi/o proteins/phospholipase C/IP3/Ca(2+) rise in MDA-MB-231 breast cancer cells.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyoung-Pil
authors.initials: KP
authors.lastname: Lee
authors.forename: Saeromi
authors.initials: S
authors.lastname: Kang
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D009928:Organ Specificity; D010755:Organophosphates / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; C095004:ADGRE5 protein, human; D015703:Antigens, CD; D001896:Boron Compounds; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007555:Isoxazoles; D008246:Lysophospholipids; D010755:Organophosphates; D011422:Propionates; D011725:Pyridines; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; C529824:VPC32183; C008301:lysophosphatidylethanolamine; C109986:2-aminoethoxydiphenyl borate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C032881:lysophosphatidic acid; D002118:Calcium
keywords: (S)-Phosphoric acid mono-{2-octadec-9-enoylamino-3-[4-(pyridin-2-ylmethoxy)-phenyl]-propyl} ester; 2-APB; 2-aminoethoxydiphenylborane; 3-(4-[4-([1-(2-Chlorophenyl)ethoxy]carbonylamino)-3-methyl-5-isoxazolyl]benzylthio) propanoic acid; Breast; G-protein-coupled receptor; GPCR; IP(3); Ki16425; LPA; LPA(1); LPA(2); LPA(3); LPA(4); LPA(5); LPA(6); LPE; LPG; LPS; Lysophosphatidic acid; Lysophosphatidylethanolamine; PTX; Receptor; VPC32183; inositol 1,4,5-trisphosphate; lysophosphatidic acid; lysophosphatidic acid receptor 3 (EDG7); lysophosphatidic acid receptor 5 (GPR92); lysophosphatidic acid receptor 6 (P2Y5); lysophosphatidic acid receptor type 1 (EDG2); lysophosphatidic acid receptor type 2 (EDG4); lysophosphatidic acid receptor type 4 (GPR23); lysophosphatidylethanolamine; lysophosphatidylglycerol; lysophosphatidylserine; pertussis toxin