Lysophosphatidylethanolamine utilizes LPA(1) and CD97 in MDA-MB-231 breast cancer cells

Cell Signal. 2013 Nov;25(11):2147-54. doi: 10.1016/j.cellsig.2013.07.001. Epub 2013 Jul 6.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Boron Compounds / pharmacology
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Isoxazoles / pharmacology
  • Lysophospholipids / metabolism*
  • Organ Specificity
  • Organophosphates / pharmacology
  • Pertussis Toxin / pharmacology
  • Propionates / pharmacology
  • Pyridines / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid / antagonists & inhibitors
  • Receptors, Lysophosphatidic Acid / genetics*
  • Receptors, Lysophosphatidic Acid / metabolism
  • Signal Transduction
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism

Substances

  • 3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid
  • ADGRE5 protein, human
  • Antigens, CD
  • Boron Compounds
  • Inositol 1,4,5-Trisphosphate Receptors
  • Isoxazoles
  • Lysophospholipids
  • Organophosphates
  • Propionates
  • Pyridines
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • VPC32183
  • lysophosphatidylethanolamine
  • 2-aminoethoxydiphenyl borate
  • Pertussis Toxin
  • Type C Phospholipases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • lysophosphatidic acid
  • Calcium