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Potential roles for prions and protein-only inheritance in cancer

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Abstract

Inherited mutations are known to cause familial cancers. However, the cause of sporadic cancers, which likely represent the majority of cancers, is yet to be elucidated. Sporadic cancers contain somatic mutations (including oncogenic mutations); however, the origin of these mutations is unclear. An intriguing possibility is that a stable alteration occurs in somatic cells prior to oncogenic mutations and promotes the subsequent accumulation of oncogenic mutations. This review explores the possible role of prions and protein-only inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast, have identified a large number of proteins as prions that confer dominant phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have mammalian functional homologs. The human prion protein (PrP) is known to cause neurodegenerative diseases and has now been found to be upregulated in multiple cancers. PrP expression in cancer cells contributes to cancer progression and resistance to various cancer therapies. Epigenetic changes in the gene expression and hyperactivation of MAP kinase signaling, processes that in lower eukaryotes are affected by prions, play important roles in oncogenesis in humans. Prion phenomena in yeast appear to be influenced by stresses, and there is considerable evidence of the association of some amyloids with biologically positive functions. This suggests that if protein-only somatic inheritance exists in mammalian cells, it might contribute to cancer phenotypes. Here, we highlight evidence in the literature for an involvement of prion or prion-like mechanisms in cancer and how they may in the future be viewed as diagnostic markers and potential therapeutic targets.

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Acknowledgments

The authors gratefully acknowledge research grant funding from the Australian Research Council (ARC DP110100389) to ALM, MQW, and YOC; the National Health and Medical Research Council (Program Grant ID: 442903) to KK; a Dr. Jian Zhou Smart State Fellowship (Queensland State Government), the NH&MRC, and Cancer Council Queensland to MQW; and the National Institutes of Health (R01GM58763) to YOC.

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Authors and Affiliations

  1. School of Medical Science and Molecular Basis of Disease Programme, Griffith Health Institute, Griffith University, Parklands Drive, Southport, Queensland, 4222, Australia

    H. Antony, M. Q. Wei & A. L. Munn

  2. Signal Transduction Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland, 4006, Australia

    A. P. Wiegmans & K. K. Khanna

  3. School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA, 30332-0230, USA

    Y. O. Chernoff

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  1. H. Antony
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Correspondence to K. K. Khanna or A. L. Munn.

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H. Antony and A. P. Wiegmans made an equal contribution.

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Antony, H., Wiegmans, A.P., Wei, M.Q. et al. Potential roles for prions and protein-only inheritance in cancer. Cancer Metastasis Rev 31, 1–19 (2012). https://doi.org/10.1007/s10555-011-9325-9

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