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Cyclin K dependent regulation of Aurora B affects apoptosisand proliferation by induction of mitotic catastrophe inprostate cancer

Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostatecancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance ofCyclin K as a biomarker for patients with prost...

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Main Authors: Schecher, Sabrina (Author) , Walter, Britta (Author) , Falkenstein, Michael (Author) , Macher-Göppinger, Stephan (Author) , Hadaschik, Boris (Author) , Duensing, Stefan (Author) , Roth, Wilfried (Author) , Tagscherer, Katrin (Author)
Format: Article (Journal)
Language:English
Published: 3 July 2017
In: International journal of cancer
Year: 2017, Volume: 141, Issue: 8, Pages: 1643-1653
ISSN:1097-0215
DOI:10.1002/ijc.30864
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1002/ijc.30864
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Author Notes:Sabrina Schecher, Britta Walter, Michael Falkenstein, Stephan Macher-Goeppinger, Philipp Stenzel, Kristina Krümpelmann, Boris Hadaschik, Sven Perner, Glen Kristiansen, Stefan Duensing, Wilfried Roth and Katrin E. Tagscherer
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Summary:Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostatecancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance ofCyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells inducesapoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown ofCyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate aCyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction ofmitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence-free survivalin patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promis-ing anti-cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in pros-tate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome andtherapy response for patients with prostate cancer.
Item Description:Gesehen am 17.04.2018
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.30864

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