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Cyclin K dependent regulation of Aurora B affects apoptosis and proliferation by induction of mitotic catastrophe in prostate cancer
Author(s) -
Schecher Sabrina,
Walter Britta,
Falkenstein Michael,
MacherGoeppinger Stephan,
Stenzel Philipp,
Krümpelmann Kristina,
Hadaschik Boris,
Perner Sven,
Kristiansen Glen,
Duensing Stefan,
Roth Wilfried,
Tagscherer Katrin E.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30864
Subject(s) - prostate cancer , cyclin b , mitotic catastrophe , cancer research , cyclin , cyclin b1 , cell cycle , cyclin a , mitosis , cancer , cyclin e , cyclin d , cancer cell , biology , cyclin d1 , cell growth , medicine , microbiology and biotechnology , cyclin dependent kinase 1 , genetics
Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostate cancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance of Cyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells induces apoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown of Cyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate a Cyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction of mitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence‐free survival in patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promising anti‐cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in prostate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome and therapy response for patients with prostate cancer.