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

被引:87
作者
Maquoi, E
Noël, A
Frankenne, F
Angliker, H
Murphy, G
Foidart, JM
机构
[1] Univ Liege, Lab Biol Tumeurs & Dev, B-4000 Liege, Belgium
[2] Friedrich Miescher Inst, CH-4002 Basel, Switzerland
[3] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
关键词
membrane type 1 matrix metalloproteinase; matrix metalloproteinase 2; furin; activation; tumor cell; invasion;
D O I
10.1016/S0014-5793(98)00187-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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, me 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, (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:262 / 266
页数:5
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