Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase gamma in human melanoma cells.
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
Lee
Hoi Young
HY
College of Medicine, Konyang University, 320-711, Nonsan, South Korea.
Bae
Gyu Un
GU
Jung
In Duk
ID
Lee
Jang Soon
JS
Kim
Yong Kee
YK
Noh
Sung Hoon
SH
Stracke
Mary L
ML
Park
Chang Gyo
CG
Lee
Hyang Woo
HW
Han
Jeung Whan
JW
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D058544:Class Ib Phosphatidylinositol 3-Kinase; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009097:Multienzyme Complexes; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000494:pharmacology; D043264:Phosphodiesterase I; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010727:Phosphoric Diester Hydrolases; D021122:Protein Subunits; D011755:Pyrophosphatases; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin; D000099189:Lysophospholipase D
D000730:Androstadienes; D002867:Chromones; D058544:Class Ib Phosphatidylinositol 3-Kinase; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D007527:Isoenzymes; D009025:Morpholines; D009097:Multienzyme Complexes; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D043264:Phosphodiesterase I; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010727:Phosphoric Diester Hydrolases; D021122:Protein Subunits; D011755:Pyrophosphatases; D010566:Virulence Factors, Bordetella; D000077191:Wortmannin; D000099189:Lysophospholipase D; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546760:PIK3CG protein, human