Laboratory of Cancer Metabolism, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
Laboratory of Cancer Metabolism, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; at the Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA; and at the Unit of Biochemistry, Department of Physiological Sciences II, Faculty of Medicine, Campus Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
Nat Rev Cancer. 2018 Jan;18(1):51-63. doi: 10.1038/nrc.2017.104. Epub 2017 Dec 1.
The ribosome is a complex molecular machine composed of numerous distinct proteins and nucleic acids and is responsible for protein synthesis in every living cell. Ribosome biogenesis is one of the most multifaceted and energy- demanding processes in biology, involving a large number of assembly and maturation factors, the functions of which are orchestrated by multiple cellular inputs, including mitogenic signals and nutrient availability. Although causal associations between inherited mutations affecting ribosome biogenesis and elevated cancer risk have been established over the past decade, mechanistic data have emerged suggesting a broader role for dysregulated ribosome biogenesis in the development and progression of most spontaneous cancers. In this Opinion article, we highlight the most recent findings that provide new insights into the molecular basis of ribosome biogenesis in cancer and offer our perspective on how these observations present opportunities for the design of new targeted cancer treatments.
核糖体是一种由众多不同蛋白质和核酸组成的复杂分子机器,负责每个活细胞中的蛋白质合成。核糖体生物发生是生物学中最多样化和最耗能的过程之一,涉及大量的组装和成熟因子,其功能由多种细胞输入协调,包括有丝分裂信号和营养物质的可用性。尽管过去十年已经确定了影响核糖体生物发生的遗传突变与癌症风险升高之间的因果关系,但出现的机制数据表明,失调的核糖体生物发生在大多数自发性癌症的发展和进展中起着更广泛的作用。在这篇观点文章中,我们强调了提供有关癌症中核糖体生物发生分子基础的新见解的最新发现,并就这些观察结果为设计新的靶向癌症治疗方法提供了机会提出了我们的看法。