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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.
AuthorsSoo-Jin Park, Kyoung-Pil Lee, Saeromi Kang, Hae-Young Chung, Yoe-Sik Bae, Fumikazu Okajima, Dong-Soon Im
JournalCellular signalling (Cell Signal) Vol. 25 Issue 11 Pg. 2147-54 (Nov 2013) ISSN: 1873-3913 [Electronic] England
PMID23838008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013.
Chemical References
  • 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
Topics
  • Antigens, CD (genetics, metabolism)
  • Boron Compounds (pharmacology)
  • Calcium (metabolism)
  • Cell Line, Tumor
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go (antagonists & inhibitors, genetics, metabolism)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors (antagonists & inhibitors, genetics, metabolism)
  • Isoxazoles (pharmacology)
  • Lysophospholipids (metabolism)
  • Organ Specificity
  • Organophosphates (pharmacology)
  • Pertussis Toxin (pharmacology)
  • Propionates (pharmacology)
  • Pyridines (pharmacology)
  • RNA, Small Interfering (genetics, metabolism)
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid (antagonists & inhibitors, genetics, metabolism)
  • Signal Transduction
  • Type C Phospholipases (antagonists & inhibitors, genetics, metabolism)

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