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- Title
Mitosis Phase Enrichment with Identification of Mitotic Centromere-Associated Kinesin As a Therapeutic Target in Castration-Resistant Prostate Cancer.
- Authors
Sircar, Kanishka; Heng Huang; Limei Hu; Yuexin Liu; Dhillon, Jasreman; Cogdell, David; Aprikian, Armen; Efstathiou, Eleni; Navone, Nora; Troncoso, Patricia; Wei Zhang
- Abstract
The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason-grade hormone-sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy-resistant CRPC samples (n = 25) was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10) and hormone-sensitive prostate cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapyresistant disease. The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target.
- Subjects
PROSTATE cancer; MITOSIS; DRUG therapy; CASTRATION; GENE expression; PROTEINS
- Publication
PLoS ONE, 2012, Vol 7, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0031259