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.