eIF-4E expression and its role in malignancies and metastases.
The contribution of the mRNA cap-binding protein, eIF-4E, to malignant transformation and progression has been illuminated over the past decade. eIF-4E overexpression has been demonstrated in human tumors of the breast, head and neck, colon, prostate, bladder, cervix and lung, and has been related to disease progression. Overexpression of eIF-4E in experimental models dramatically alters cellular morphology, enhances proliferation and induces cellular transformation, tumorigenesis and metastasis. Conversely, blocking eIF-4E function by expression of antisense RNA, or overexpression of the inhibitory eIF-4E binding proteins (4E-BPs), suppresses cellular transformation, tumor growth, tumor invasiveness and metastasis. Although eIF-4E regulates the recruitment of mRNA to ribosomes, and thereby globally regulates cap-dependent protein synthesis, eIF-4E contributes to malignancy by selectively enabling the translation of a limited pool of mRNAs--those that generally encode key proteins involved in cellular growth, angiogenesis, survival and malignancy (e.g. cyclin D1, c-myc, vascular endothelial growth factor, matrix metalloprotease 9). A deeper understanding of the role of eIF-4E in regulating the translation of the diverse gene products involved in all aspects of malignancy will improve the capacity to exploit eIF-4E as a therapeutic target and as a marker for human cancer progression.
De Benedetti
Arrigo
A
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130, USA. adeben@lsuhsc.edu
Graff
Jeremy R
JR
D000818:Animals; D002471:Cell Transformation, Neoplastic; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D009955:Ornithine Decarboxylase / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D009955:Ornithine Decarboxylase