Urokinase receptor interacts with alpha(v)beta(5) vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer(441 views) Carriero M, Del Vecchio S, Capozzoli M, Franco P, Fontana L, Zannetti A, Botti G, D'Aiuto G, Salvatore M, Stoppelli M
Cancer Res (ISSN: 0008-5472, 1538-7445, 1538-7445electronic), 1999 Oct 15; 59(20): N/D-N/D.
Paper type: Journal Article, Abstract, Conference,
Impact factor: 8.614, 5-year impact factor: 8.036
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Urokinase receptor interacts with alpha(v)beta(5) vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer
Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion, Recent studies indicate that, the urokinase receptor (uPAR) is associated in large molecular complexes with other molecules, such as integrins. To test the possibility that uPAR may physically and functionally interact with vitronectin (Vn) receptors, we determined the expression level of uPAR, alpha(v)beta(3), and alpha(v)beta(5) Vn receptors in 10 human breast carcinomas. Here, we show the ability of uPAR to physically associate with alpha(v)beta(5) in the breast carcinomas examined. The functional effects of this interaction were studied using HT1080 human fibrosarcoma and MCF-7 human breast carcinoma cell Lines, both exhibiting a urokinase-dependent physical association between uPAR and alpha(v)beta(5). Both cell lines respond to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that are mediated by alpha(v)beta(5) and require protein kinase C activity. On the contrary, binding of Vn to alpha(v)beta(5) results in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, alpha(v)beta(5) is required for urokinase-directed, receptor-dependent MCF-7 and HT1080 cell migration. These data show that uPAR association with alpha(v)beta(5) leads to a functional interaction of these receptors and suggest that uPAR directs cytoskeletal rearrangements and cell migration by altering alpha(v)beta(5) signaling specificity.
Urokinase receptor interacts with alpha(v)beta(5) vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer