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.