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The Emerging Role for the mRNA Cap-Binding Protein, EIF-4E, in Metastatic Progression

  • Chapter
Cancer Metastasis — Related Genes

Part of the book series: Cancer Metastasis — Biology and Treatment ((CMBT,volume 3))

Summary

The successful evolution of metastases requires the interplay of numerous and diverse gene products-metalloproteases (MMP-9), adhesion factors (CD44v6), apoptosis suppressors (bcl-2), angiogenesis factors (VEGF), and proto-oncoproteins (c-myc, cyclin D1). Expression of each of these potent proteins is profoundly influenced by the activity of the mRNA cap-binding protein, eIF-4E. Indeed, eIF-4E overexpression has been shown to selectively influence a wide array of key proteins including c-myc, cyclin D1, VEGF, bFGF, CD44v6, MMP-9 and nm23. By selectively and coordinately upregulating expression of these potent proteins, enhanced eIF-4E activity, which characterizes a variety of human tumors and has been associated with malignant progression, can drive metastatic progression. As such, eIF-4E represents a potential convergence point whereby many key metastasis genes are regulated and may therefore represent a novel, compelling target for therapeutic intervention. Indeed, blocking eIF-4E activity dramatically suppresses malignancy by specifically suppressing the expression of key malignancy-related genes like cyclin D1, bFGF, VEGF and ODC (47 and references therein). Blocking eIF-4E activity has also recently been shown to induce apoptosis (109). Indeed, eIF-4E may be an attractive new therapeutic target precisely because each and every function necessary for the evolution and growth of a metastatic nodule is mediated or influenced by a gene product that is regulated translationally. The development of novel reagents to interfere with eIF-4E and translation initiation may provide a very promising alternative to current anti-cancer therapies.

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Authors and Affiliations

  1. L.P. Markey Cancer Center, University of Kentucky, Dept. of Microbiology and Immunology, Lexington, KY

    Stephen G. Zimmer

  2. Lilly Research Labs, Cancer Research Division, Eli Lilly and Company, Indianapolis, IN

    Jeremy R. Graff

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  1. Stephen G. Zimmer
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  2. Jeremy R. Graff
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  1. Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Pennsylvania, USA

    Danny R. Welch

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© 2002 Kluwer Academic Publishers

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Zimmer, S.G., Graff, J.R. (2002). The Emerging Role for the mRNA Cap-Binding Protein, EIF-4E, in Metastatic Progression. In: Welch, D.R. (eds) Cancer Metastasis — Related Genes. Cancer Metastasis — Biology and Treatment, vol 3. Springer, Dordrecht. https://doi.org/10.1007/0-306-47821-8_14

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  • DOI: https://doi.org/10.1007/0-306-47821-8_14

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-0522-0

  • Online ISBN: 978-0-306-47821-5

  • eBook Packages: Springer Book Archive

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