Autotaxin promotes the expression of matrix metalloproteinase-3 via activation of the MAPK cascade in human fibrosarcoma HT-1080 cells.
Autotaxin (ATX) is an approximately 125-kDa transmembrane protein that is considered to be a tumor progression factor based on its lysophospholipase D activity. Here, we report that lysophosphatidic acid produced by ATX promotes the secretion of matrix metalloproteinase-3 (MMP3) from the human fibrosarcoma cell line HT-1080. The c-Jun N-terminal kinases (JNKs) and c-Jun of HT-1080 cells were rapidly phosphorylated after ATX treatment. A specific JNK inhibitor also exhibited this activation of signaling molecules and MMP3 expression. The present results suggest a novel function of ATX in promoting MMP3 production via the mitogen-activated protein kinase cascade, thereby stimulating tumor cell invasiveness.
Haga
Arayo
A
Gifu Prefectural Research Institute for Health and Environmental Science, Naka-Fudougaoka, Kakamigahara, Japan. haga-arayo@pref.gifu.lg.jp
Nagai
Hiroyuki
H
Deyashiki
Yoshihiro
Y
D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D043264:Phosphodiesterase I / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011755:Pyrophosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation; D000099189:Lysophospholipase D
D048031:JNK Mitogen-Activated Protein Kinases; D008246:Lysophospholipids; D019278:Matrix Metalloproteinase 3; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D047428:Protein Kinase Inhibitors; D011755:Pyrophosphatases; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000099189:Lysophospholipase D; C511768:MMP3 protein, human; C032881:lysophosphatidic acid