Impact of pim kinases and c-myc on the translational machinery in prostate cancer cells

Protein synthesis is one of the most energy consuming process in the cell and it has a major role in the regulation of gene expression. Many signaling pathways converge on components of the translational apparatus to regulate their function and alterations in the protein synthesis control contribute to diverse human diseases, including cancer. The transcriptional factor c-myc and the oncogenic Pim kinases are implicated in promoting cell growth and protein synthesis. A strong sinergy between Pim kinases and c-myc has been observed in prostate cancer cells. The molecular mechanism underlying their synergy is not completely understood. We have observed that both c-myc and Pim kinases induce an increase in the general protein synthesis and in the 4E-BP1 phosphorylation. In addition, Pim kinases overexpression induces an increase in AKT (Ser 473) and S6K (Thr 389) phosphorylation, two proteins involved in the translational control. Conversely, c-myc overexpression causes a downregulation of the phosphorylation level of these proteins. Our preliminary results suggest that the changes induced by Pim kinases could depend on some upstream alterations such as at the level of RTKs. Instead, the effects induced by c-myc could be explained by the activity of the phosphatase PP2A. However, because malignant cells exhibit augmented activity of most of the components of the translational machinery, it is supposed that they became "addicted" to elevated protein synthesis. Targeting Pim kinases and c-myc could be an effective strategy to reduce the higher activity of the translational machinery that characterize cancer cells. In fact, we found that depletion of c-myc and Pim kinases together induce a stronger decrease in the general protein synthesis. Our results reveal new informations about the cooperation of these two proteins in PCa, suggesting new druggable targets for a therapeutic approach.