Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis.
Recent studies have implicated the mRNA cap-binding protein, eIF-4E, as a key regulator of malignant progression. Indeed, the major intracellular signaling pathways involved in tumor growth and malignancy, the MAP kinase and PI3 kinase pathways, induce eIF-4E activity. Furthermore, immunohistochemical analyses have revealed that eIF-4E is overexpressed and related to disease progression in human cancers of the colon, head and neck, and breast. In experimental tumors, manipulation of eIF-4E function profoundly affects not only tumorigenesis but also tumor invasion and metastasis. While increasing global protein synthesis rates, the increased activity of eIF-4E that typifies both human and experimental tumors disproportionately enhances the translation of a specific array of potent growth regulatory and malignancy-related proteins, including c-myc, cyclin D1, ornithine decarboxylase, vascular endothelial growth factor, basic fibroblast growth factor and others. Herein, we review the data supporting the notion that, by coordinately upregulating the translation of numerous malignancy-related proteins, eIF-4E plays a pivotal role in regulating not only tumor growth, but also invasion and metastasis.
University of Kentucky, Lucille P. Markey Cancer Center, Department of Microbiology and Immunology, Lexington 40536, USA.
S G
SG
Zimmer
A
A
DeBenedetti
J R
JR
Graff
D002471:Cell Transformation, Neoplastic; D039561:Eukaryotic Initiation Factor-4E; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000502:physiology*; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins / Q000502:physiology*; D015854:Up-Regulation
D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins