1. Academic Validation
  2. 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

  • J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433.
Gongping Gu 1 Dejian Zhao Ziming Yin Ping Liu
Affiliations

Affiliation

  • 1 Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu 210097, PR China.
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.

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