Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance.
Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance.
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DOI：
10.1158/0008-5472.can-21-4087
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发表时间：
2022-07-05
期刊：
影响因子：
11.2
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中科院分区：
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核糖体是 rRNA 和核糖体蛋白的复杂集合，充当 mRNA 翻译机器。核糖体生物发生是一个多步骤的过程，从核仁开始并在细胞质中结束。该过程受到多个检查点和监视路径的严格控制。这些检查点和通路的扰动可能导致核糖体生物发生的过度激活。新出现的证据表明，癌细胞含有一类特殊的核糖体（癌核糖体），可促进致癌翻译程序、调节细胞功能并促进代谢重连。核糖体蛋白、rRNA 加工和核糖体组装因子的突变会导致核糖体病，而核糖体病与罹患恶性肿瘤的风险增加相关。最近的研究将核糖体蛋白突变和异常核糖体与不良预后联系起来，强调核糖体靶向治疗是治疗癌症患者的一种有前途的方法。在这里，我们总结了核糖体生物合成失调的各个方面以及由此产生的癌核糖体对恶性肿瘤行为、治疗耐药性和临床结果的影响。核糖体生物发生是一个有前途的治疗靶点，了解这一过程的重要决定因素将有助于改进并可能选择性地针对核糖体生物合成的治疗策略。
Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is a multistep process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoint and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyperactivation of ribosome biogenesis. Emerging evidence suggests that cancer cells harbor a specialized class of ribosomes (onco-ribosomes) that facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring. Mutations in ribosomal proteins, rRNA processing, and ribosome assembly factors result in ribosomopathies that are associated with an increased risk of developing malignancies. Recent studies have linked mutations in ribosomal proteins and aberrant ribosomes with poor prognosis, highlighting ribosome-targeted therapy as a promising approach for treating patients with cancer. Here, we summarize various aspects of dysregulation of ribosome biogenesis and the impact of resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, and clinical outcome. Ribosome biogenesis is a promising therapeutic target, and understanding the important determinants of this process will allow for improved and perhaps selective therapeutic strategies to target ribosome biosynthesis.