Our overall objective will be to identify genes or sets of genes that are up- or down-regulated in association with metastasis and putatively involved in cell polarity/motility/migration and define (a) which affect metastatic progression in vivo and (b) what effects they have on aspects of cell motility in vitro. That will allow initial correlations between individual molecules, aspects of cell motility and metastasis. The data from those biological assays will then be analyzed in quantitative, computational models to make predictions about how motility is controlled and about connections between specific molecules or sets of molecules, components of motility and metastatic progression in vivo. Those predictions will be tested by interventions (overexpression, inhibition, RNA interference, mutation) in the cellular and animal models. That in turn will lead to refinements of the models. We expect, by this cycle of experimental measurements, modeling, validation and refinement, to generate robust models of the changes in cell motility that contribute to invasion and metastasis. Such insights should lead to new approaches to diagnosis, management and treatment of metastatic disease.
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