Arfaptin 1 inhibits ADP-ribosylation factor-dependent matrix metalloproteinase-9 secretion induced by phorbol ester in HT 1080 fibrosarcoma cells.
Matrix metalloproteinase-9 (MMP-9) is a collagenolytic enzyme secreted by cancer cells and involved in invasiveness and metastasis. Its secretion from human fibrosarcoma HT 1080 cells is markedly enhanced by phorbol 12-myristate 13-acetate (PMA) and abolished by brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) activation. These results support a role for ARF in PMA-stimulated MMP-9 secretion. Overexpression of arfaptin 1, a 39 kDa ARF-binding protein that inhibits in vitro activation of cholera toxin ADP-ribosyltransferase and phospholipase D (PLD) by ARF, inhibited PMA-stimulated MMP-9 and PLD activation. These data are in agreement with previous results demonstrating a significant role for PLD in regulating MMP-9 secretion.
Ho
Wan-Ting
WT
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 38232-0295, USA.
Exton
John H
JH
Williger
Ben-Tsion
BT
D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors*; D048868:Adaptor Proteins, Signal Transducing; D020126:Brefeldin A / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005354:Fibrosarcoma; D006801:Humans; D007700:Kinetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C105088:ARFIP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020126:Brefeldin A; D020780:Matrix Metalloproteinase 9; D020727:ADP-Ribosylation Factors; D013755:Tetradecanoylphorbol Acetate