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相分离在癌症中的作用:从影响和机制到治疗潜力。

Phase separation in Cancer: From the Impacts and Mechanisms to Treatment potentials.

机构信息

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.

Hunan Key Laboratory of Translational Radiation Oncology, 283 Tongzipo Road, Changsha 410013, Hunan, China.

出版信息

Int J Biol Sci. 2022 Aug 1;18(13):5103-5122. doi: 10.7150/ijbs.75410. eCollection 2022.

Abstract

Cancer is a public health problem of great concern, and it is also one of the main causes of death in the world. Cancer is a disease characterized by dysregulation of diverse cellular processes, including avoiding growth inhibitory factors, avoiding immune damage and promoting metastasis, etc. However, the precise mechanism of tumorigenesis and tumor progression still needs to be further elucidated. Formations of liquid-liquid phase separation (LLPS) condensates are a common strategy for cells to achieve diverse functions, such as chromatin organization, signal transduction, DNA repair and transcriptional regulation, etc. The biomolecular aggregates formed by LLPS are mainly driven by multivalent weak interactions mediated by intrinsic disordered regions (IDRs) in proteins. In recent years, aberrant phase separations and transition have been reported to be related to the process of various diseases, such as neurodegenerative diseases and cancer. Herein, we discussed recent findings that phase separation regulates tumor-related signaling pathways and thus contributes to tumor progression. We also reviewed some tumor virus-associated proteins to regulate the development of virus-associated tumors via phase separation. Finally, we discussed some possible strategies for treating tumors by targeting phase separation.

摘要

癌症是一个备受关注的公共卫生问题,也是世界上主要的死亡原因之一。癌症是一种疾病,其特征是多种细胞过程失调,包括逃避生长抑制因子、逃避免疫损伤和促进转移等。然而,肿瘤发生和肿瘤进展的确切机制仍需要进一步阐明。液-液相分离(LLPS)凝聚物的形成是细胞实现多种功能的一种常见策略,如染色质组织、信号转导、DNA 修复和转录调控等。LLPS 形成的生物分子聚集体主要由蛋白质中固有无序区域(IDR)介导的多价弱相互作用驱动。近年来,有报道称异常的相分离和转变与神经退行性疾病和癌症等多种疾病的发生过程有关。在此,我们讨论了最近的发现,即相分离调节与肿瘤相关的信号通路,从而促进肿瘤的进展。我们还回顾了一些肿瘤病毒相关蛋白通过相分离来调节病毒相关肿瘤的发展。最后,我们讨论了一些通过靶向相分离来治疗肿瘤的可能策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c7a/9379413/ddc38284d492/ijbsv18p5103g001.jpg

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