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. Our work in the second project period has defined and performed detailed analysis of the HEF1-AurA-Ajuba complex. This has allowed us to develop a model in which HEF1 and AurA mutually stabilize each other, and HEF1 and Ajuba synergize to promote AurA activation at mitotic entry. At mitotic exit, phosphorylation by AurA promotes HEF1 return to focal adhesions. Excess of HEF1 protects AurA from inhibition by targeted small molecule inhibitors. In the past two years, elevation of HEF1 has been established as important for metastasis and/or invasion in lung cancer, melanoma, and glioblastoma; our ongoing work on this project will determine whether this is also true for ovarian cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2007
- Accession Number
- ADA483168
Entities
People
- Erica Golemis