Oncotarget

Research Papers:

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

Wookyeom Yang, Hanbyoul Cho, Ha-Yeon Shin, Joon-Yong Chung, Eun Suk Kang, Eun-ju Lee and Jae-Hoon Kim _

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Oncotarget. 2016; 7:49481-49497. https://doi.org/10.18632/oncotarget.10373

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Abstract

Wookyeom Yang1,2,*, Hanbyoul Cho1,2,*, Ha-Yeon Shin1,2, Joon-Yong Chung3, Eun Suk Kang4, Eun-ju Lee1,2, Jae-Hoon Kim1,2

1Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

2Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Korea

3Tissue Array Research Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

4Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

*These authors contributed equally to this work

Correspondence to:

Jae-Hoon Kim, email: jaehoonkim@yuhs.ac

Keywords: Cdk1, cytoplasmic accumulation, epithelial ovarian cancer, RO-3306

Received: October 05, 2015     Accepted: June 16, 2016     Published: July 01, 2016

ABSTRACT

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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