Journal
ONCOGENE
Volume 33, Issue 9, Pages 1124-1134Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.51
Keywords
PTOV1; c-Jun; translation; prostate cancer; invasion
Funding
- Ministry of Science and Innovation
- MINECO [SAF2008-03936, SAF2011-30496]
- TV3 Telemarathon
- Instituto Carlos III [RD06/0020/0058 RETICS]
- AGAUR [2009SGR1482]
- Red Nacional de Biobancos, Instituto Carlos III
- Fondo de Investigaciones de la Seguridad Social [PI20231]
- [SAF2008-04136-C02-01]
- [SAF2011-24686]
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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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