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Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1

Academic Article
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Overview

authors

  • Hama, K.
  • Aoki, J.
  • Fukaya, M.
  • Kishi, Y.
  • Sakai, T.
  • Suzuki, R.
  • Ohta, H.
  • Yamori, T.
  • Watanabe, M.
  • Chun, Jerold
  • Arai, H.

publication date

  • April 2004

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Autotaxin (ATX) is a tumor cell motility-stimulating factor originally isolated from melanoma cell supernatant that has been implicated in regulation of invasive and metastatic properties of cancer cells. Recently, we showed that ATX is identical to lysophospholipase D, which converts lysophosphatidylcholine to a potent bioactive phospholipid mediator, lysophosphatidic acid (LPA), raising the possibility that autocrine or paracrine production of LPA by ATX contributes to tumor cell motility. Here we demonstrate that LPA and ATX mediate cell motility-stimulating activity through the LPA receptor, LPA(1). In fibroblasts isolated from lpa(1)(-/-) mice, but not from wild-type or lpa(2)(-/-), cell motility stimulated with LPA and ATX was completely absent. In the lpa(1)(-/-) cells, LPA-stimulated lamellipodia formation was markedly diminished with a concomitant decrease in Rac1 activation. LPA stimulated the motility of multiple human cancer cell lines expressing LPA(1), and the motility was attenuated by an LPA(1)-selective antagonist, Ki16425. The present study suggests that ATX and LPA(1) represent potential targets for cancer therapy.

subject areas

  • Animals
  • Calcium
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cells, Cultured
  • Chemotaxis
  • Dose-Response Relationship, Drug
  • Fibroblasts
  • Glucose-6-Phosphate Isomerase
  • Glycoproteins
  • Isoxazoles
  • Lysophospholipids
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Models, Biological
  • Multienzyme Complexes
  • Neoplasms
  • Phosphodiesterase I
  • Phosphoric Diester Hydrolases
  • Platelet-Derived Growth Factor
  • Propionates
  • Pyrophosphatases
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Skin
  • Time Factors
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258 (Print) 0021-9258 (Linking)

Digital Object Identifier (DOI)

  • 10.1074/jbc.M313927200

PubMed ID

  • 14744855
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Additional Document Info

start page

  • 17634

end page

  • 17639

volume

  • 279

issue

  • 17

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