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Ezrin mediates c-Myc actions in prostate cancer cell invasion

Oncogene volume 29, pages 1531–1542 (2010)Cite this article

Abstract

The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals involve the modulation of Akt and GSK-3β activity resulting in increased c-Myc protein synthesis and inhibition of its degradation. In summary, we have shown a key role for ezrin as a mediator of c-Myc-induced tumorigenesis in prostate cancer cells.

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Acknowledgements

We thank Maria Henriksson for providing the c-Myc expression plasmid. The work carried out in this study was in part supported by the Novo Nordisk Foundation Center for Protein Research, Karolinska Institutet, Cancerfonden (45576-B01-01XAB), Swedish Research Council (VR- 529-2002-6766) and the Robert Lundberg Memorial Foundation (2007Lund0045).

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Authors and Affiliations

  1. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

    Y-C Chuan, D Iglesias-Gato & G Norstedt

  2. Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark

    Y-C Chuan & A Flores-Morales

  3. Department of Clinical Sciences, University of Las Palmas de GC, Las Palmas, Spain

    L Fernandez-Perez

  4. Canary Institute for Cancer Research, Las Palmas, Spain

    L Fernandez-Perez

  5. Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden

    A Cedazo-Minguez

  6. Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    S-T Pang

  7. Andrology Center, Karolinska Institute, Stockholm, Sweden

    Å Pousette

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  1. Y-C Chuan
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Correspondence to Y-C Chuan.

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

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Chuan, YC., Iglesias-Gato, D., Fernandez-Perez, L. et al. Ezrin mediates c-Myc actions in prostate cancer cell invasion. Oncogene 29, 1531–1542 (2010). https://doi.org/10.1038/onc.2009.442

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