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Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1

Oncogene volume 33, pages 1124–1134 (2014)Cite this article

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Abstract

Prostate tumor overexpressed-1 (PTOV1), a modulator of the Mediator transcriptional regulatory complex, is expressed at high levels in prostate cancer and other neoplasias in association with a more aggressive disease. Here we show that PTOV1 interacts directly with receptor of activated protein C kinase 1 (RACK1), a regulator of protein kinase C and Jun signaling and also a component of the 40S ribosome. Consistent with this interaction, PTOV1 was associated with ribosomes and its overexpression promoted global protein synthesis in prostate cancer cells and COS-7 fibroblasts in a mTORC1-dependent manner. Transfection of ectopic PTOV1 enhanced the expression of c-Jun protein without affecting the levels of c-Jun or RACK1 mRNA. Conversely, knockdown of PTOV1 caused significant declines in global protein synthesis and c-Jun protein levels. High levels of PTOV1 stimulated the motility and invasiveness of prostate cancer cells, which required c-Jun, whereas knockdown of PTOV1 strongly inhibited the tumorigenic and metastatic potentials of PC-3 prostate cancer cells. In human prostate cancer samples, the expression of high levels of PTOV1 in primary and metastatic tumors was significantly associated with increased nuclear localization of active c-Jun. These results unveil new functions of PTOV1 in the regulation of protein translation and in the progression of prostate cancer to an invasive and metastatic disease.

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Acknowledgements

We thank A. Esquerra, T. Moliné and P. Guijarro for excellent technical help, J.J. Lozano for help with statistical analysis and J. Reventós for advice and support. This study was supported by Ministry of Science and Innovation and MINECO SAF2008-03936, SAF2011-30496, TV3 Telemarathon, and Instituto Carlos III RD06/0020/0058 RETICS (to RP); SAF2008-04136-C02-01 and SAF2011-24686 (to TMT); AGAUR 2009SGR1482 (to RP and TMT); Red Nacional de Biobancos, Instituto Carlos III (to RB); and Fondo de Investigaciones de la Seguridad Social PI20231 (to PLF).

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  1. N Marqués and M Sesé: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Unit in Biomedicine, Translational and Pediatrics Oncology, Vall d’Hebron Institute of Research, Universidad Autónoma, Barcelona, Spain

    N Marqués, M Sesé, V Cánovas, F Valente & R Paciucci

  2. Department of Cell Biology, Institute for Molecular Biology, CSIC, Barcelona, Spain

    R Bermudo, T Celià-Terrassa & T M Thomson

  3. Department of Pathology and Tumour Bank, Human and Experimental Functional Oncomorphology, Hospital Clínic—Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

    R Bermudo & P L Fernández

  4. Department of Pathology, Vall d’Hebron Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain

    I de Torres & S Ramón y Cajal

  5. Functional Validation and Preclinical Research, Molecular Imaging Platform CIBBIM-Nanomedicine, Vall d’Hebron Institut de Recerca, Barcelona, Spain

    Y Fernández & I Abasolo

  6. Department of Physiology and Biophysics, Laboratory of Molecular and Cellular Andrology, Faculty of Medicine, University of Chile, Santiago, Chile

    H Contreras & E Castellón

  7. Institute for Research in Biomedicine, Parc Científic, University of Barcelona, Barcelona, Spain

    R Méndez

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Marqués, N., Sesé, M., Cánovas, V. et al. Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1. Oncogene 33, 1124–1134 (2014). https://doi.org/10.1038/onc.2013.51

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