Griffith Health Institute, Griffith University, Southport, Queensland, Australia.
Cancer Metastasis Rev. 2012 Jun;31(1-2):1-19. doi: 10.1007/s10555-011-9325-9.
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.
遗传性突变已知会导致家族性癌症。然而，散发性癌症（可能代表大多数癌症）的病因尚未阐明。散发性癌症包含体细胞突变（包括致癌突变）；然而，这些突变的起源尚不清楚。一个有趣的可能性是，致癌突变之前，体细胞中发生了稳定的改变，并促进了随后致癌突变的积累。这篇综述探讨了朊病毒和仅蛋白质遗传在癌症中的可能作用。使用低等真核生物（主要是酵母）进行的遗传研究已经确定了大量作为朊病毒的蛋白质，这些蛋白质赋予具有细胞质（非孟德尔）遗传的显性表型。其中许多具有哺乳动物功能同源物。已知人类朊病毒蛋白（PrP）会导致神经退行性疾病，现在已在多种癌症中发现其表达上调。癌细胞中 PrP 的表达有助于癌症的进展和对各种癌症治疗的耐药性。基因表达的表观遗传变化和 MAP 激酶信号的过度激活，在低等真核生物中受朊病毒影响的过程，在人类肿瘤发生中起着重要作用。酵母中的朊病毒现象似乎受到应激的影响，并且有相当多的证据表明一些淀粉样蛋白与生物学上的积极功能有关。这表明，如果仅蛋白质体细胞遗传存在于哺乳动物细胞中，它可能会导致癌症表型。在这里，我们强调了文献中涉及朊病毒或朊病毒样机制在癌症中的作用的证据，以及它们将来如何被视为诊断标志物和潜在的治疗靶点。
