Lost in translation: dysregulation of cap-dependent translation and cancer.
Activation of the phosphatidylinositol 3' kinase-Akt pathway has long been associated with malignant transformation and antiapoptotic signaling. Mutations downstream of Akt that activate the TOR kinase are found in tumor-prone syndromes, while overexpression of translation initiation complex components, such as eIF4E, occurs frequently in human cancer. However, direct roles for TOR signaling or eIF4E overexpression, in the genesis of cancer, have been lacking. Recent papers, including one by in this issue of Cancer Cell, clearly establish that dysregulation of cap-dependent translation confers malignant characteristics and induces cancer by suppressing apoptosis, underscoring the potential of therapeutics that selectively target the Akt-TOR-eIF4E pathway.
Bjornsti
Mary-Ann
MA
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105, USA.
Houghton
Peter J
PJ
D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D029701:Saccharomyces cerevisiae Proteins; C403503:FAM107A protein, human; C083324:TOR1 protein, S cerevisiae