Li Lingwei, Yao Litong, Wang Mozhi, Zhou Xiang, Xu Yingying
Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Biochim Biophys Acta Rev Cancer. 2024 Nov;1879(6):189206. doi: 10.1016/j.bbcan.2024.189206. Epub 2024 Nov 9.
Phase separation, a process in which biomolecules segregate into distinct liquid-like compartments within cells, has recently been identified as a crucial regulator of various cellular functions, including the DNA damage response (DDR). Dysregulation of phase separation may contribute to genomic instability, oncogenesis, and tumor progression. However, the specific roles and mechanisms underlying phase separation remain largely elusive. This comprehensive review aims to elucidate the complex relationship between phase separation and the DDR in the context of cancer biology. We focus on the molecular mechanisms underlying phase separation and its role in orchestrating DDR signaling and repair processes. Additionally, we discuss how the dysregulation of phase separation in cancer cells impacts genome stability, tumorigenesis, and therapeutic responses. By leveraging the unique properties of phase separation in the DDR, researchers can potentially advance basic research and develop personalized cancer therapies targeting the dysregulated biomolecular condensates that drive tumorigenesis.
相分离是一种生物分子在细胞内分离成不同的类液体区室的过程,最近已被确定为各种细胞功能的关键调节因子,包括DNA损伤反应(DDR)。相分离失调可能导致基因组不稳定、肿瘤发生和肿瘤进展。然而,相分离背后的具体作用和机制在很大程度上仍然难以捉摸。这篇全面的综述旨在阐明癌症生物学背景下相分离与DDR之间的复杂关系。我们关注相分离背后的分子机制及其在协调DDR信号传导和修复过程中的作用。此外,我们讨论癌细胞中相分离失调如何影响基因组稳定性、肿瘤发生和治疗反应。通过利用DDR中相分离的独特特性,研究人员有可能推进基础研究,并开发针对驱动肿瘤发生的失调生物分子凝聚物的个性化癌症治疗方法。