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Miscellaneous

Emerging therapeutic targets in oncology: urokinase-type plasminogen activator system

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Pages 109-133 | Published online: 25 Feb 2005

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  • •Presents evidence that uPA binding to uPAR activates intra-cellular kinases, and that cleavage of the uPAR between DI and D2/3 is required for activity. Given that the uPAR does not have an intracellular domain, these data suggest that an-other molecular entity is responsible for the transduction of this signal.
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  • •A nice review of the evidence that, upon binding of PAT-1 to uPA/uPAR, the complex is internalized and degraded, re-sulting in unbound uPAR being recycled to the cell-surface. This observation may underlie the mechanism of uPA's role in cellular migration.
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  • ••A very nice review of the interactions of uPA, uPAR, PAT-1and the integrins, and their roles in cellular migration.
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  • •Provides direct evidence of the role of uPA in the biological response to infection by pathogens.
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  • •Provides direct evidence that uPA plays a key role in a model of human angiogenesis.
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  • •Provides evidence that uPA functions in two separate path-ways to control angiogenesis.
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  • •Provides direct evidence that uPA plays a role in the pro-gression of tumours.
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  • •Provides evidence, using enzymatically inactive uPA, that the enzymatic activity is key in the progression of cancer.
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  • •A recent review of the clinical evidence that the uPA system is correlated with poor prognosis in breast cancer.
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  • ••Provides evidence that PAI-1 directly plays a role in the pro-gression of cancer. This observation is counterintuitive to its role as a plasminogen activator inhibitor and is very important.
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  • ••Provides direct evidence that PAT-1 governs the balance be-tween cellular adhesion and detachment and may play a key role in cellular migration.
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  • •Provides evidence that uPAR interacts directly with integrins and regulates their function.
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  • •Provides evidence that PAT-1 is required to initiate the inter-nalisation of uPA/uPAR resulting in the re-expression of un-bound uPAR on the cell surface, and perhaps being responsible for cellular migration.
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