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.

Local drug delivery based on nanoparticles (NP) represents a novel strategy to improve inner ear treatments. The intratympanic delivery of NP may be suitable to treat or prevent hearing loss originating from damage to hair cells and spiral ganglion neurons in the cochlea. Numerous experimental studies support in vitro and in vivo the biocompatibility of NP, their physical stability, target specificity, cell/tissue uptake and ability to internalize therapeutic agents. The topical use of NP helps to reduce the amount of drug required and avoid systemic side effects. This review focuses on recent findings and applications of different NP systems locally delivered to the inner ear. The perspectives for clinical application of NP in inner ear drug delivery are also discussed

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