Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein
| Autor: | Rafael Fridman, Rosemarie Chirco, Hyeong Reh Choi Kim, Ki Kyung Jung, Xu Wen Liu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cell Survival
Integrin Down-Regulation Apoptosis Platelet Membrane Glycoproteins CD49c Article General Biochemistry Genetics and Molecular Biology Cell Line Cell membrane Antigens CD Two-Hybrid System Techniques Cell Adhesion medicine Humans Mammary Glands Human Cell adhesion Molecular Biology Gene Library Matrigel Tissue Inhibitor of Metalloproteinase-1 General Immunology and Microbiology biology Tetraspanin 30 Integrin beta1 General Neuroscience Cell Membrane Cell Polarity Membrane Proteins Epithelial Cells Molecular biology Cell biology medicine.anatomical_structure Integrin alpha M biology.protein Integrin beta 6 Signal transduction Protein Binding Signal Transduction |
| Zdroj: | The EMBO Journal. 25:3934-3942 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7601281 |
| Popis: | This study identified CD63, a member of the tetraspanin family, as a TIMP-1 interacting protein by yeast two-hybrid screening. Immunoprecipitation and confocal microscopic analysis confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells. TIMP-1 expression correlated with the level of active integrin beta1 on the cell surface independent of cell adhesion. While MCF10A cells within a three-dimensional (3D) matrigel matrix form polarized acinar-like structures, TIMP-1 overexpression disrupted breast epithelial cell polarization and inhibited caspase-mediated apoptosis in centrally located cells, necessary for the formation and maintenance of the hollow acinar-like structures. Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface, TIMP-1 co-localization with integrin beta1, and consequently reversed TIMP-1-mediated integrin beta1 activation, cell survival signaling and apoptosis inhibition. CD63 downregulation also restored polarization and apoptosis of TIMP-1 overexpressing MCF10A cells within a 3D-matrigel matrix. Taken together, the present study identified CD63 as a cell surface binding partner for TIMP-1, regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex. |
| Databáze: | OpenAIRE |
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