Protein translation by ribosomes is one of the most energetically costly cellular processes. Consequently, the number and activity of ribosomes in cells and tissues are precisely tailored to match metabolic demands. While ribosomal proteins (RPs) play essential roles in facilitating and regulating the translation of mRNA transcripts into protein, there is increasing evidence that free RPs not bound to ribosomes can play important roles in cellular regulation. Often, free RPs act as tumour suppressors by multiple mechanisms, for example, by inducing cell cycle arrest through their ability to bind and inhibit MDM2-mediated p53 degradation. Dysregulation of these RPs, however, can result in various diseases like Diamond-Blackfan anemia, ribosomopathies, and other diseases. In cancer, epigenetic modifications, altered transcription, and processing defects in the rRNAs create “onco-ribosomes” that strongly support tumour cell replication, invasion and metastasis. In this context, free RPs in tumour cells (often mutated or post-translationally modified) further promote tumour cell proliferation, invasion, and metastasis. This review focuses specifically on extra-ribosomal roles for RPs, where depending upon cellular context, they act outside of the ribosome to either suppress tumorigenesis in normal tissues or promote tumour proliferation and progression. This new understanding of the interplay between RPs and pathways suppressing or promoting tumorigenesis further emphasizes why the ribosome is increasingly being seen as an important therapeutic target in human cancers.
核糖体介导的蛋白质翻译是细胞中能量消耗最高的过程之一。因此，细胞和组织中核糖体的数量与活性被精确调控以适应代谢需求。虽然核糖体蛋白在促进和调控mRNA转录本翻译为蛋白质的过程中发挥关键作用，但越来越多的证据表明，未与核糖体结合的自由核糖体蛋白在细胞调控中同样具有重要作用。自由核糖体蛋白常通过多种机制发挥肿瘤抑制作用，例如通过结合并抑制MDM2介导的p53降解从而诱导细胞周期停滞。然而，这些核糖体蛋白的失调可能导致多种疾病，如戴蒙德-布莱克范贫血、核糖体病及其他疾病。在癌症中，rRNA的表观遗传修饰、转录改变及加工缺陷会形成"癌性核糖体"，强力支持肿瘤细胞的复制、侵袭和转移。在此背景下，肿瘤细胞中的自由核糖体蛋白（常发生突变或翻译后修饰）会进一步促进肿瘤细胞增殖、侵袭和转移。本综述聚焦于核糖体蛋白的核糖体外功能，根据细胞环境的不同，它们可在核糖体外发挥抑制正常组织肿瘤发生或促进肿瘤增殖与进展的作用。对核糖体蛋白与抑癌/促癌通路相互作用的新认识，进一步揭示了核糖体日益成为人类癌症重要治疗靶点的深层机制。
肿瘤(癌症)患者之家