title: BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity.
abstract: 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 3D 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.
authors: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu 210097, PR China.
authors: Gongping
authors: G
authors: Gu
authors: Dejian
authors: D
authors: Zhao
authors: Ziming
authors: Z
authors: Yin
authors: Ping
authors: P
authors: Liu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D048708:Cell Growth Processes; D002460:Cell Line; D002465:Cell Movement; D058851:GPI-Linked Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D017434:Protein Structure, Tertiary; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2