A wealth of novel findings, including congenital ribosomal mutations in ribosomopathies and somatic ribosomal mutations in various cancers, have significantly increased our understanding of the relevance of ribosomes in oncogenesis. Here, we explore the growing list of mechanisms by which the ribosome is involved in carcinogenesis—from the hijacking of ribosomes by oncogenic factors and dysregulated translational control, to the effects of mutations in ribosomal components on cellular metabolism. Of clinical importance, the recent success of RNA polymerase inhibitors highlights the dependence on “onco-ribosomes” as an Achilles' heel of cancer cells and a promising target for further therapeutic intervention.

Significance: The recent discovery of somatic mutations in ribosomal proteins in several cancers has strengthened the link between ribosome defects and cancer progression, while also raising the question of which cellular mechanisms such defects exploit. Here, we discuss the emerging molecular mechanisms by which ribosomes support oncogenesis, and how this understanding is driving the design of novel therapeutic strategies. Cancer Discov; 7(10); 1–19. ©2017 AACR.

大量的新发现，包括核糖体病中的先天性核糖体突变和各种癌症中的体细胞核糖体突变，显着增加了我们对核糖体在肿瘤发生中的相关性的理解。在这里，我们探索了越来越多的核糖体参与癌变的机制——从致癌因素劫持核糖体和翻译控制失调，到核糖体成分突变对细胞代谢的影响。具有临床重要性的是，RNA聚合酶抑制剂最近的成功凸显了对“癌核糖体”的依赖，这是癌细胞的致命弱点，也是进一步治疗干预的有希望的目标。

意义：最近在几种癌症中发现的核糖体蛋白体细胞突变加强了核糖体缺陷与癌症进展之间的联系，同时也提出了此类缺陷利用哪种细胞机制的问题。在这里，我们讨论核糖体支持肿瘤发生的新兴分子机制，以及这种理解如何推动新型治疗策略的设计。癌症发现；7(10)；1-19。©2017 AACR。