The Cap-dependent Translation Apparatus Integrates and Amplifies Cancer Pathways

Deregulation of a plethora of cancer genes causes pathological changes in only a small set of pathways that confer a cell with malignant properties. This principle of convergence of oncogenic signaling-the ability of several hundred oncogenes to focus their effects on a few critical regulatory nodes that impart autonomy to the cell-motivates the search for putative focal points. Genomic, transcriptional and posttranslational mechanisms that regulate the function of cancer gene pathways are all well established. It has recently become evident that cancer is also subject to translational control. Here we discuss cancer-related regulatory events that are mediated by the cap-dependent mRNA binding stage of translation initiation. This information implicates the cap-dependent protein synthesis pathway as a pleotropic integrator and amplifier of many essential oncogenic signals, and the translational control network as a bona fide molecular target for anti-cancer therapeutic interventions.