Hwang Sseu-Pei, Denicourt Catherine
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
NAR Cancer. 2024 Apr 15;6(2):zcae017. doi: 10.1093/narcan/zcae017. eCollection 2024 Jun.
The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome biogenesis, notably through RNA Pol I inhibition, elicits a stress response marked by nucleolar integrity loss, and subsequent G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, rendering ribosomal RNA synthesis a potential therapeutic vulnerability. The review further explores targeting ribosome biogenesis vulnerabilities as a promising strategy to disrupt global ribosome production, presenting therapeutic opportunities for cancer treatment.
核糖体生物合成失调是癌症的一个标志，有助于适应肿瘤进展各个方面所必需的翻译需求变化。本综述探讨了核糖体生物合成与癌症发展之间的复杂相互作用，强调了关键致癌信号通路所精心编排的动态调控。最近的研究揭示了核糖体的多方面作用，其作用范围不仅限于蛋白质工厂，还包括在mRNA翻译中的调控功能。核糖体生物合成失调不仅阻碍了对全局蛋白质生产和增殖的精确控制，还影响诸如维持干细胞样特性和上皮-间质转化等过程，促进癌症进展。干扰核糖体生物合成，特别是通过抑制RNA聚合酶I，会引发以核仁完整性丧失为特征的应激反应，随后导致G1期细胞周期停滞或细胞死亡。这些发现表明癌细胞可能依赖增强的RNA聚合酶I转录，使核糖体RNA合成成为一个潜在的治疗弱点。该综述进一步探讨了将核糖体生物合成弱点作为一种有前景的策略来破坏全局核糖体生产，为癌症治疗提供了治疗机会。
