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Translation factors and ribosomal proteins control tumor onset and progression: how?

Oncogene volume 33, pages 2145–2156 (2014)Cite this article

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Abstract

Gene expression is shaped by translational control. The modalities and the extent by which translation factors modify gene expression have revealed therapeutic scenarios. For instance, eukaryotic initiation factor (eIF)4E activity is controlled by the signaling cascade of growth factors, and drives tumorigenesis by favoring the translation of specific mRNAs. Highly specific drugs target the activity of eIF4E. Indeed, the antitumor action of mTOR complex 1 (mTORc1) blockers like rapamycin relies on their capability to inhibit eIF4E assembly into functional eIF4F complexes. eIF4E biology, from its inception to recent pharmacological targeting, is proof-of-principle that translational control is druggable. The case for eIF4E is not isolated. The translational machinery is involved in the biology of cancer through many other mechanisms. First, untranslated sequences on mRNAs as well as noncoding RNAs regulate the translational efficiency of mRNAs that are central for tumor progression. Second, other initiation factors like eIF6 show a tumorigenic potential by acting downstream of oncogenic pathways. Third, genetic alterations in components of the translational apparatus underlie an entire class of inherited syndromes known as ‘ribosomopathies’ that are associated with increased cancer risk. Taken together, data suggest that in spite of their evolutionary conservation and ubiquitous nature, variations in the activity and levels of ribosomal proteins and translation factors generate highly specific effects. Beside, as the structures and biochemical activities of several noncoding RNAs and initiation factors are known, these factors may be amenable to rational pharmacological targeting. The future is to design highly specific drugs targeting the translational apparatus.

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Acknowledgements

We apologize to those whose work we were unable to cite. This work is supported by grants AIRC IG 2011, AIRC 5 × mille, AICR 13-0045 and Fondazione Buzzi to SB, AIRC IG 10653 to FL, PRIN 20104AE23N to SB and FL.

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  1. Department of Biology, University ‘Tor Vergata’, Roma, Italy

    F Loreni

  2. San Raffaele Scientific Institute, Ospedale San Raffaele, Milan, Italy

    M Mancino & S Biffo

  3. DISIT, Alessandria, Italy

    M Mancino & S Biffo

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Loreni, F., Mancino, M. & Biffo, S. Translation factors and ribosomal proteins control tumor onset and progression: how?. Oncogene 33, 2145–2156 (2014). https://doi.org/10.1038/onc.2013.153

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