Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells.
Autotaxin (ATX) is a strong motogen that can increase invasiveness and angiogenesis. In the present study, we investigated the signal transduction mechanism of ATX-induced tumor cell motility. Unlike N19RhoA expressing cells, the cells expressing N17Cdc42 or N17Rac1 showed reduced motility against ATX. ATX activated Cdc42 and Rac1 and increased complex formation between these small G proteins and p21-activated kinase (PAK). Furthermore, ATX phosphorylated focal adhesion kinase (FAK) that was not shown in cells expressing dominant negative mutants of Cdc42 or Rac1. Collectively, these data strongly indicate that Cdc42 and Rac1 are essential for ATX-induced tumor cell motility in A2058 melanoma cells, and that PAK and FAK might be also involved in the process.
Jung
In Duk
ID
College of Medicine, Konyang University, 320-711, Nonsan, South Korea.
Lee
Jangsoon
J
Yun
Seong Young
SY
Park
Chang Gyo
CG
Choi
Wahn Soo
WS
Lee
Hyang Woo
HW
Choi
Oksoon H
OH
Han
Jeung Whan
JW
Lee
Hoi Young
HY
D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism; D005799:Genes, Dominant; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008545:Melanoma / Q000378:metabolism*; D009097:Multienzyme Complexes; D009154:Mutation; D037342:Pertussis Toxin / Q000494:pharmacology; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011755:Pyrophosphatases; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D000099189:Lysophospholipase D
D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D009097:Multienzyme Complexes; D037342:Pertussis Toxin; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011505:Protein-Tyrosine Kinases; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D000099189:Lysophospholipase D; C496050:PTK2 protein, human