Inhibition of matrix metalloproteinase 2 maturation and HT1080 invasiveness by a synthetic furin inhibitor
Inhibition of matrix metalloproteinase 2 maturation and HT1080 invasiveness by a synthetic furin inhibitor
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DOI：
10.1016/s0014-5793(98)00187-2
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发表时间：
1998-03-13
期刊：
影响因子：
3.5
通讯作者：
Foidart, JM
中科院分区：
文献类型：
--
作者：
Maquoi, E;Noël, A;Foidart, JM
在各种肿瘤中观察到的基质金属蛋白酶 2 (MMP-2) 激活与转移进展之间的密切相关性表明 MMP-2 是触发肿瘤扩散的“主开关”。最近，1 型膜 MMP (MT1-MMP) 被确定为 MMP-2 的潜在生理激活剂。与所有其他 MMP 一样，MT1-MMP 具有一个前结构域，该酶必须将其除去才能获得其催化潜力。前结构域末端存在弗林蛋白酶样转化酶的典型识别基序 (RXKR)，表明这些蛋白酶在 MT1-MMP 加工中具有潜在作用。为了评估弗林蛋白酶在前 MT1-MMP 加工中的影响，我用合成弗林蛋白酶抑制剂处理 HT1080 细胞，并监测其激活 pro-MMP-2 的能力及其侵袭潜力，我们的结果表明，弗林蛋白酶抑制剂降低了 pro-MT1-MMP 加工以及 pro-MMP-2 激活和细胞侵袭性，因此，我们的数据进一步证明弗林蛋白酶是与肿瘤细胞侵袭和转移潜力相关的 MMP 成熟的关键因素，(C) 1998 年欧洲生化学会联合会。
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.