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.
Highlights
Cyclin-dependent kinases (CDKs) are important cell cycle-regulating proteins, which belong to a serine/ threonine kinase family that comprise of a catalytic kinase subunit, together with cyclin protein partners
It is possible that the high activity of cytoplasmic Cyclin dependent kinase 1 (Cdk1) in ovarian cancer depends on cytoplasmic cyclins and reduced inhibitory phosphorylation
There is whether cytoplasmic cdk1 which was elevated in the ovarian cancer can have activity, or not
Summary
Cyclin-dependent kinases (CDKs) are important cell cycle-regulating proteins, which belong to a serine/ threonine kinase family that comprise of a catalytic kinase subunit, together with cyclin protein partners. Only Cdk , and 6 are directly involved in the cell cycle, and of these, Cdk , and 6 are not essential to the cell cycle. Unlike other Cdks, Cdk can promote the cell cycle alone and is essential for cell cycle progression and cell division [1,2,3]. Cdk regulates the G2 phase as part of a complex with cyclin A and is involved in G2/M transition by forming a complex with cyclin B. Knockdown of Cdk increases G2/M arrest during the cell cycle and results in polyploid cells [1, 2, 4]
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