Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2022-07-08 , DOI: 10.1038/s41392-022-01076-x Xuhui Tong 1, 2 , Rong Tang 3, 4 , Jin Xu 1, 2 , Wei Wang 1, 2 , Yingjun Zhao 5 , Xianjun Yu 1, 2 , Si Shi 3, 4
Liquid–liquid phase separation (LLPS) is a novel principle for explaining the precise spatial and temporal regulation in living cells. LLPS compartmentalizes proteins and nucleic acids into micron-scale, liquid-like, membraneless bodies with specific functions, which were recently termed biomolecular condensates. Biomolecular condensates are executors underlying the intracellular spatiotemporal coordination of various biological activities, including chromatin organization, genomic stability, DNA damage response and repair, transcription, and signal transduction. Dysregulation of these cellular processes is a key event in the initiation and/or evolution of cancer, and emerging evidence has linked the formation and regulation of LLPS to malignant transformations in tumor biology. In this review, we comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant LLPS. In addition, we discuss the therapeutic perspectives of LLPS in cancer research and the most recently developed drug candidates targeting LLPS modulation that can be used to combat tumorigenesis.
中文翻译:
肿瘤生物学中的液-液相分离
液-液相分离 (LLPS) 是解释活细胞中精确时空调节的新原理。LLPS 将蛋白质和核酸分隔成具有特定功能的微米级、液体状、无膜体,最近被称为生物分子凝聚体。生物分子凝聚体是各种生物活动的细胞内时空协调的执行者,包括染色质组织、基因组稳定性、DNA 损伤反应和修复、转录和信号转导。这些细胞过程的失调是癌症发生和/或演变的关键事件,新出现的证据表明 LLPS 的形成和调节与肿瘤生物学中的恶性转化有关。在这篇评论中,我们全面总结了生物分子凝聚物形成和生物物理功能的详细机制,并回顾了最近在阐明由异常 LLPS 驱动的癌细胞病理学所涉及的多种机制方面取得的重大进展。此外,我们还讨论了 LLPS 在癌症研究中的治疗前景,以及最近开发的靶向 LLPS 调节的候选药物,可用于对抗肿瘤发生。