BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity.
BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity.
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DOI：
10.1002/jcb.23433
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发表时间：
2012-03
影响因子：
4
通讯作者：
Liu, Ping
中科院分区：
文献类型：
--
作者：
Gu, Gongping;Zhao, Dejian;Yin, Ziming;Liu, Ping
MT 1-MMP（膜型1-基质金属蛋白酶）通过介导MMP 2/明胶酶A和包括I型胶原在内的多种底物的切割，在细胞生长和肿瘤侵袭中发挥重要作用。BST-2（骨髓基质细胞抗原2）是一种膜系链蛋白，其表达可显著减少包括HIV在内的多种包膜病毒从感染细胞中的释放。本研究证明瞬时和IFN-α诱导的BST-2均能通过与细胞内MT 1-MMP的C-末端结合，抑制其蛋白水解活性，从而降低MMP-2的活性，最终抑制细胞的生长和迁移。酶谱和Western-blot实验表明BST-2可降低MMP 2活性，但对MMP 2和MT 1-MMP基因表达无影响。共聚焦和免疫沉淀结果显示BST-2与MT 1-MMP共定位并相互作用。这种相互作用抑制了MT 1-MMP的蛋白水解酶活性，并阻断了proMMP 2的活化。MT 1-MMP C端缺失突变体与BST-2共转染后，MMP-2活性无明显变化，突变体与BST-2之间无相互作用。说明MT 1-MMP的C端在与BST-2的相互作用中起关键作用。此外，BST-2抑制细胞在三维I型胶原凝胶晶格中的生长和细胞迁移。综上所述，BST-2作为一种膜蛋白和包膜病毒的系链蛋白，是一种新型的MT 1-MMP抑制剂，在临床上作为肿瘤细胞生长和迁移的抑制剂具有重要的应用价值。
MT1-MMP (membrane type 1-matrix metalloproteinase) plays important roles in cell growth and tumor invasion via mediating cleavage of MMP2/gelatinase A and a variety of substrates including type I collagen. BST-2 (bone marrow stromal cell antigen 2) is a membrane tetherin whose expression dramatically reduces the release of a broad range of enveloped viruses including HIV from infected cells. In this study, we provided evidence that both transient and IFN-α induced BST-2 could decrease the activity of MMP2 via binding to cellular MT1-MMP on its C- terminus and inhibiting its proteolytic activity; and finally block cell growth and migration. Zymography gel and Western-blot experiments demonstrated that BST-2 decreased MMP2 activity, but no effect on the expression of MMP2 and MT1-MMP genes. Confocal and immunoprecipitation data showed that BST-2 co-localized and interacted with MT1-MMP. This interaction inhibited the proteolytic enzyme activity of MT1-MMP, and blocked the activation of proMMP2. Experimental results of C-terminus deletion mutant of MT1-MMP showed that activity of MMP2 was no change and also no interaction existed between the mutant and BST-2 after co-transfection with the mutant and BST-2. It meant that C-terminus of MT1-MMP played a key role in the interaction with BST-2. In addition, cell growth in 3-D type I collagen gel lattice and cell migration were all inhibited by BST-2. Taken together, BST-2, as a membrane protein and a tetherin of enveloped viruses, was a novel inhibitor of MT1-MMP and could be considerable as an inhibitor of cancer cell growth and migration on clinic.
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影响因子：
11.4
作者：
Bravo-Cordero, Jose J.;Marrero-Diaz, Raquel;Montoya, Maria C.
通讯作者：
Montoya, Maria C.
影响因子：
64.5
作者：
Hiraoka, N;Allen, E;Weiss, SJ
通讯作者：
Weiss, SJ
影响因子：
4
作者：
Remacle, A;Murphy, G;Roghi, C
通讯作者：
Roghi, C
影响因子：
5.6
作者：
Liu, Ping;Yang, Jianbo;Pei, Jing;Pei, Duanqing;Wilson, Michael J.
通讯作者：
Wilson, Michael J.
DOI：
10.1083/jcb.200108112
发表时间：
2001-12-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Uekita T;Itoh Y;Yana I;Ohno H;Seiki M
通讯作者：
Seiki M