Translational control of cell proliferation and viability in normal and neoplastic cells

Available evidence indicates that the initiation step in translation of mRNA into protein-a step mediated by the translational complex eIF4F-is an obligatory regulatory hub in the circuitry of the normal cell physiology and cancer. Control of cell cycle progression, apoptosis, premature cell senescence and authophagy by eIF4F is required in the developmental and physiological setting for maintenance of cell homeostasis, whereas usurping eIF4F-mediated translational control is oncogenic. The members of eIF4F are ubiquitously dysregulated or overexpressed in human malignancies. When hyperactivated by upstream oncogenic signaling, eIF4F selectively stimulates translation of a group of mRNAs required for the acquisition and maintenance of the basic capabilities of cancer, including cell autonomy for growth signals, tissue invasion and evasion of cancer defense systems, such as apoptosis and premature senescence. These findings place aberrant eIF4F in a list of primary candidates for targeting by cancer therapy.