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Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase gamma in human melanoma cells.

Abstract
Autotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, stimulates tumor cell motility at sub-nanomolar levels and augments invasiveness and angiogenesis. We investigated the role of G protein-coupled phosphoinositide 3-kinase gamma (PI3Kgamma) in ATX-mediated tumor cell motility stimulation. Pretreatment of human melanoma cell line A2058 with wortmannin or LY294002 inhibited ATX-induced motility. ATX increased the PI3K activity in p110gamma, but not p85, immunoprecipitates. This effect was abrogated by PI3K inhibitors or inhibited by pertussis toxin. Furthermore, stimulation of tumor cell motility by ATX was inhibited by catalytically inactive form of PI3Kgamma, strongly indicating the crucial role of PI3Kgamma for ATX-mediated motility in human melanoma cells
AuthorsHoi Young Lee, Gyu Un Bae, In Duk Jung, Jang Soon Lee, Yong Kee Kim, Sung Hoon Noh, Mary L Stracke, Chang Gyo Park, Hyang Woo Lee, Jeung Whan Han
JournalFEBS letters (FEBS Lett) Vol. 515 Issue 1-3 Pg. 137-40 (Mar 27 2002) ISSN: 0014-5793 [Print] Netherlands
PMID11943209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Androstadienes
  • Chromones
  • Enzyme Inhibitors
  • Glycoproteins
  • Isoenzymes
  • Morpholines
  • Multienzyme Complexes
  • Protein Subunits
  • Virulence Factors, Bordetella
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Pertussis Toxin
  • Phosphatidylinositol 3-Kinases
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • GTP-Binding Proteins
  • Pyrophosphatases
  • Glucose-6-Phosphate Isomerase
  • wortmannin
Topics
  • Androstadienes (pharmacology)
  • Animals
  • COS Cells
  • Cell Movement (drug effects)
  • Chromones (pharmacology)
  • Class Ib Phosphatidylinositol 3-Kinase
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • GTP-Binding Proteins (metabolism)
  • Glucose-6-Phosphate Isomerase (pharmacology)
  • Glycoproteins (pharmacology)
  • Humans
  • Isoenzymes (antagonists & inhibitors, metabolism, pharmacology)
  • Melanoma (drug therapy, metabolism)
  • Morpholines (pharmacology)
  • Multienzyme Complexes
  • Pertussis Toxin
  • Phosphatidylinositol 3-Kinases (antagonists & inhibitors, metabolism, pharmacology)
  • Phosphodiesterase I
  • Phosphoric Diester Hydrolases
  • Protein Subunits
  • Pyrophosphatases
  • Tumor Cells, Cultured
  • Virulence Factors, Bordetella (pharmacology)

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