Translational control of cell fate: from integration of environmental signals to breaching anticancer defense.

Despite their genetic diversity, different cancers manifest common features at the protein pathway level. They share a core group of perturbed pathways that converge upon a few regulatory hubs linking the cellular signaling network with the basic metabolic machinery. Available evidence indicates that one such hub is the eIF4F-mediated cap-dependent mRNA translation initiation apparatus, whose integrity is required for physiological control of growth, proliferation and viability. However, when hyperactivated by upstream oncogenic signaling, eIF4F selectively stimulates the translation of a group of mRNAs required for cancer genesis and progression. Here, we describe a model that links the pro-neoplastic function of eIF4F to its ability to disable oncogene-activated tumor surveillance programs and propose a novel therapeutic strategy for cancer based upon targeting aberrant eIF4F with small-molecule antagonists.