Inhibition of matrix metalloproteinase 2 maturation and HT1080 invasiveness by a synthetic furin inhibitor

FEBS Letters

Noël, Agnès²  Frankenne, Francis²  Foidart, Jean-Michel²  Maquoi, Erik²  Murphy, Gillian³  Angliker, Herbert¹ 

[1] Friedrich Institut, Basel, Switzerland;Laboratoire de Biologie des Tumeurs et du Développement, Université de Liège, Tour de Pathologie (B23), Sart Tilman, B-4000 Liège, Belgium;School of Biological Sciences, University of East Anglia, Norwich, UK

关键词: Membrane type 1 matrix metalloproteinase;    Matrix metalloproteinase 2;    Furin;    Activation;    Tumor cell;    Invasion;    BM;    basement membrane;    ECM;    extracellular matrix;    mAb;    monoclonal antibody;    MMP;    matrix metalloproteinase;    MT1-MMP;    membrane type 1 MMP;    TIMP;    tissue inhibitor of metalloproteinase;    TPA;    12-O-tetradecanoyl-phorbol 13-acetate;   

DOI  :  10.1016/S0014-5793(98)00187-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The close correlation observed between matrix metalloproteinase 2 (MMP-2) activation and metastatic progression in various tumors suggests that MMP-2 is a `master switch' triggering tumor spread. Recently, membrane type 1 MMP (MT1-MMP) was identified as a potential physiological activator of MMP-2. Like all other MMPs, MT1-MMP possesses a pro-domain which must be removed for the enzyme to acquire its catalytic potential. The presence of a typical recognition motif (RXKR) for the furin-like convertases at the end of its pro-domain suggests a potential role for these proteinases in MT1-MMP processing. In order to evaluate the implication of furin in pro-MT1-MMP processing, we treated HT1080 cells with a synthetic furin inhibitor and monitored their ability to activate pro-MMP-2 as well as their invasive potential. Our results demonstrated that the furin inhibitor decreased pro-MT1-MMP processing as well as pro-MMP-2 activation and cell invasiveness. Therefore, our data bring further evidence that furin is a key factor in the maturation of MMPs associated with the invasive and metastatic potential of tumor cells.

【 授权许可】

Unknown