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Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression

Oncogene volume 28, pages 3971–3982 (2009)Cite this article

Abstract

Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell–cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of β-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of β-catenin, whereas strong nuclear accumulation of β-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the β-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.

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Acknowledgements

We thank R Kampe, B König and A Klages for their excellent technical assistance. We also thank M Schindler and H Riedesel for their assistance in generation of transgenic LPXN mice. This project was supported in part by the Forschungsförderungsprogramm of the Universitätsmedizin Göttingen (to SK), by the Deutsche Forschungsgemeinschaft (to SK KA 2946/1-1), the Deutsche Krebshilfe (to PB and SS, no. 108065) and the Horst Müggenburg and Gerhard Müggenburg-Stiftung (to PB and SS).

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  1. S Kaulfuß and S von Hardenberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Human Genetics, University of Göttingen, Göttingen, Germany

    S Kaulfuß, S von Hardenberg, A M Herr, S Wolf & P Burfeind

  2. Department of Pathology, University of Göttingen, Göttingen, Germany,

    S Schweyer

  3. Department of Medical Genetics, Medical University of Vienna, Vienna,, Austria

    F Laccone

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  1. S Kaulfuß
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Correspondence to S Kaulfuß.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Kaulfuß, S., von Hardenberg, S., Schweyer, S. et al. Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression. Oncogene 28, 3971–3982 (2009). https://doi.org/10.1038/onc.2009.254

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