Do Deregulated Cas Proteins Induce Genomic Instability In Early Stage Ovarian Cancer

摘要: Abstract : Increased genomic instability arising from centrosomal amplification has been proposed to be an important factor causing development of traits associated with highly malignant ovarian tumors, including multidrug resistance and increased tendency metastasis. This proposal addresses the hypothesized interaction between Cas proteins (HEF1 p130Cas), Aurora A (AurA) Ajuba as being likely contribute metastatic properties tumors. In this proposal, we examine tumor samples determine if expression, activated AurA, are linked, whether protein upregulation is a poor prognosis (Aim 1). We mechanism by which activate drug-mediated inactivation AurA inhibits promotion aneuploidy 2). use drug depletion experiments centrosome enhanced cellular metastasis dependent on Cas/integrin signaling, or these separable properties; evaluate combination AurA- integrin- directed therapies 3). annual report, describe significant process all Aims that validate hypothesis critical AurA-HEF1-Ajuba interactions.