prognostic significance and functional role of cep57 in prostate cancer

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ID: 175115
2015
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Abstract
We have recently shown that centrosomal protein 57 (CEP57) is overexpressed in a subset of human prostate cancers. CEP57 is involved in intracellular transport processes, and its overexpression causes mitotic defects as well as abnormal microtubule nucleation and bundling. In the present study, we further characterized the prognostic and functional role of CEP57 in prostate cancer. Unexpectedly, we found that high CEP57 expression is an independent prognostic factor for a more favorable biochemical recurrence-free survival in two large patient cohorts. To reconcile this finding with the ability of CEP57 to cause cell division errors and thus potentially promote malignant progression, we hypothesized that alterations of microtubule-associated transport processes, in particular nuclear translocation of the androgen receptor (AR), may play a role in our finding. However, CEP57 overexpression and microtubule bundling had, surprisingly, no effect on the nuclear translocation of the AR. Instead, we found a significant increase of cells with disarranged microtubules and a cellular morphology suggestive of a cytokinesis defect. Because mitotic dysfunction leads to a reduced daughter cell formation, it can explain the survival benefit of patients with increased CEP57 expression. In contrast, we show that a reduced expression of CEP57 is associated with malignant growth and metastasis. Taken together, our findings underscore that high CEP57 expression is associated with mitotic impairment and less aggressive tumor behavior. Because the CEP57-induced microtubule stabilization had no detectable effect on AR nuclear translocation, our results furthermore suggest that microtubule-targeting therapeutics used in advanced prostate cancer such as docetaxel may have modes of action that are at least in part independent of AR transport inhibition.
Reference Key
mang2015translationalprognostic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Josef Mang;Nina Korzeniewski;Dimo Dietrich;Verena Sailer;Yanis Tolstov;Sam Searcy;Jost von Hardenberg;Sven Perner;Glen Kristiansen;Alexander Marx;Wilfried Roth;Esther Herpel;Carsten Grüllich;Valentin Popeneciu;Sascha Pahernik;Boris Hadaschik;Markus Hohenfellner;Stefan Duensing
Journal advances in acoustics and vibration
Year 2015
DOI
10.1016/j.tranon.2015.11.004
URL
http://www.sciencedirect.com/science/article/pii/S1936523315300267
Keywords
neoplasms Oncology including cancer and carcinogens tumors

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