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Alternative splicing and cancer metastasis: prognostic and therapeutic applications

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Abstract

Metastatic cells exhibit an extraordinary phenotypic plasticity, not only in adapting to unfamiliar microenvironments but also in surviving aggressive treatments and immune responses. A major source of phenotypic variability is alternative splicing (AS) of the pre-messenger RNA. This process is catalyzed by one of the most complex pieces of cellular molecular regulatory events, the spliceosome, which is composed of ribonucleoproteins and polypeptides termed spliceosome factors. With strong evidence indicating that AS affects nearly all genes encoded by the human genome, aberrant AS programs have a significant impact on cancer cell development and progression. In this review, we present insights about the genomic and epigenomic factors affecting AS, summarize the most recent findings linking aberrant AS to metastatic progression, and highlight potential prognostic and therapeutic applications.

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Acknowledgements

This work was supported by the National Cancer Institute, National Institutes of Health (#R01CA167967); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the AVON Foundation Breast Cancer Crusade (#02-2015-061); the Associates for Breast and Prostate Cancer Studies (ABCs) award; and the Fashion Footwear Association of New York (FFANY) foundation award.

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  1. Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA, USA

    Diego M. Marzese, Ayla O. Manughian-Peter, Javier I. J. Orozco & Dave S. B. Hoon

  2. Sequencing Center, John Wayne Cancer Institute, Santa Monica, CA, USA

    Dave S. B. Hoon

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  1. Diego M. Marzese
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  2. Ayla O. Manughian-Peter
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  3. Javier I. J. Orozco
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  4. Dave S. B. Hoon
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Correspondence to Dave S. B. Hoon.

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Marzese, D.M., Manughian-Peter, A.O., Orozco, J.I.J. et al. Alternative splicing and cancer metastasis: prognostic and therapeutic applications. Clin Exp Metastasis 35, 393–402 (2018). https://doi.org/10.1007/s10585-018-9905-y

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