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eIF-4E expression and its role in malignancies and metastases

Oncogene volume 23, pages 3189–3199 (2004)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by Grant BCTR0100512 from the Susan G Komen Foundation.

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  1. Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport, PO Box 33932, 1501 Kings Highway, Shreveport, 71130, LA, USA

    Arrigo De Benedetti

  2. Cancer Division, Lilly Research Labs, Eli Lilly and Company, Lilly Corporate Center, DC 0546, Indianapolis, 46285, IN, USA

    Jeremy R Graff

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De Benedetti, A., Graff, J. eIF-4E expression and its role in malignancies and metastases. Oncogene 23, 3189–3199 (2004). https://doi.org/10.1038/sj.onc.1207545

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