Journal article
Aurora Kinase A Mediates Epithelial Ovarian Cancer Cell Migration and Adhesion
Oncogene, v 33(5), pp 539-549
30 Jan 2014
PMID: 23334327
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aurora kinase A (AURKA) localizes to centrosomes and mitotic spindles where it mediates mitotic progression and chromosomal stability. Overexpression of AURKA is common in cancer, resulting in acquisition of alternate non-mitotic functions. In the current study, we identified a novel role for AURKA in regulating ovarian cancer cell dissemination and evaluated the efficacy of an AURKA-selective small molecule inhibitor, alisertib (MLN8237), as a single agent and combined with paclitaxel using an orthotopic xenograft model of epithelial ovarian cancer (EOC). Ovarian carcinoma cell lines were used to evaluate the effects of AURKA inhibition and overexpression on migration and adhesion. Pharmacologic or RNAi-mediated inhibition of AURKA significantly reduced ovarian carcinoma cell migration and adhesion and the activation-associated phosphorylation of the cytoskeletal regulatory protein SRC at tyrosine 416 (pSRC
Y416
). Conversely, enforced expression of
AURKA
resulted in increased migration, adhesion and activation of SRC in cultured cells.
In vivo
tumor growth and dissemination were inhibited by alisertib treatment as a single agent. Moreover, combination of alisertib with paclitaxel, an agent commonly used in treatment of EOC, resulted in more potent inhibition of tumor growth and dissemination compared to either drug alone. Taken together, these findings support a role for AURKA in EOC dissemination by regulating migration and adhesion. They also point to the potential utility of combining AURKA inhibitors with taxanes as a therapeutic strategy for the treatment of EOC patients.
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Details
- Title
- Aurora Kinase A Mediates Epithelial Ovarian Cancer Cell Migration and Adhesion
- Creators
- Thuy-Vy Do - Fox Chase Cancer CenterFang Xiao - Fox Chase Cancer CenterLaura E. Bickel - Fox Chase Cancer CenterAndres J. Klein-Szanto - Fox Chase Cancer CenterHarsh B. Pathak - Fox Chase Cancer CenterXiang HuaCaitlin Howe - Fox Chase Cancer CenterShane O’Brien - Fox Chase Cancer CenterMarisa MaglatyJeffrey A. Ecsedy - Millennium Engineering and IntegrationSamuel Litwin - Fox Chase Cancer CenterErica A. Golemis - Fox Chase Cancer CenterRussell J. Schilder - Thomas Jefferson UniversityAndrew K. Godwin - Fox Chase Cancer CenterDenise C. Connolly - Fox Chase Cancer Center
- Publication Details
- Oncogene, v 33(5), pp 539-549
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- R01 CA136596 || CA / National Cancer Institute : NCI P30 CA006927 || CA / National Cancer Institute : NCI R01 CA140323 || CA / National Cancer Institute : NCI P50 CA083638 || CA / National Cancer Institute : NCI R01 CA063366 || CA / National Cancer Institute : NCI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000331125100002
- Scopus ID
- 2-s2.0-84895072108
- Other Identifier
- 991022008195204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology