4.3 Article

Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer

Journal

ONCOTARGET
Volume 7, Issue 31, Pages 49481-49497

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10373

Keywords

Cdk1; cytoplasmic accumulation; epithelial ovarian cancer; RO-3306

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2014R1A1A2057882]

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Cyclin dependent kinase 1 (Cdk1) have previously reported correlation with cancer growth and a key regulator for cell cycle. Mostly, Cdk1' s function of nucleus for cell cycle is well known to be associated with cancer, but cytoplasmic Cdk1's traits are not clearly identified, yet. We revealed that tissue microarray blocks of epithelial ovarian cancer (n = 249) showed increased level of cytoplasmic Cdk1 (p < 0.001), but not in nucleus (p = 0.192) of histologic cell type independently. On survival analysis, Cdk1 overexpression conferred a significantly worse prognosis in 5-year overall survival (Log-rank p = 0.028, Hazard ratio = 2.016, 95% CI = 1.097 to 4.635). Also, the expression of Cdk1 was increased in ovarian cancer cell lines and Gene Expression Omnibus datasets. When the expression and activity of Cdk1 were inhibited by si-Cdk1 or RO-3306 which is a potent Cdk1 inhibitor, the growth of ovarian cancer was diminished. Moreover, combined treatment with RO-3306 and cisplatin in ovarian cancer significantly elevated anti-cancer effects than single-agent treatment. In conclusion, cytoplasmic Cdk1 expression which was elevated in ovarian cancer predicts a poor overall survival. The inhibition of Cdk1 expression and activity reduced ovarian cancer growth.

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