Do Deregulated Cas Proteins Induce Genomic Instability in Early-Stage Ovarian Cancer
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 to metastasis. This proposal addresses the hypothesized interaction between the Cas proteins (HEF1 and p130Cas), Aurora A (AurA) and Ajuba as being likely to contribute to genomic instability and metastatic properties of ovarian tumors. In this proposal, we examine tumor samples to determine if Cas expression, activated AurA, and centrosomal amplification are linked, and whether Cas protein upregulation is associated with a poor prognosis (Aim 1). We examine the mechanism by which Cas proteins activate AurA, and determine if drug-mediated inactivation of AurA inhibits Cas promotion of aneuploidy (Aim 2). We use drug and depletion experiments to determine if centrosome amplification and enhanced cellular metastasis are linked, and dependent on Cas/integrin signaling, or whether these are separable properties; and to evaluate combination of AurA- and integrin- directed therapies (Aim 3). In this annual report, we describe significant process on all Aims that validate the hypothesis of critical AurA-HEF1-Ajuba interactions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2006
- Accession Number
- ADA483255
Entities
People
- Erica Golemis