title: Translational control of cell fate: from integration of environmental signals to breaching anticancer defense.
abstract: 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.
authors.affiliation: Department of Medicine and Masonic Cancer Center, University of Minnesota; Minneapolis, MN, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bitterman
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Polunovsky
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D016922:Cellular Senescence; D039562:Eukaryotic Initiation Factor-4F / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009857:Oncogenes; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D012333:RNA, Messenger