液-液相分离的发生机制及其在肿瘤进展中的关键作用

Mechanism of liquid-liquid phase separation and its key role in tumor progression

摘要

液-液相分离(liquid-liquid phase separation,LLPS)可以驱动细胞内蛋白质和核酸等生物大分子自发聚集,形成具有液态特性的生物分子凝聚体(biomolecular condensate,BMC)即无膜细胞器(membrane-less organelle,MLO).研究发现,关键蛋白的LLPS形成、调控及异常与肿瘤的发生、发展、转移及血管生成等过程密切相关.文章系统综述了LLPS的发生机制,并探讨了其在肿瘤进展不同阶段中的作用,以期为通过干预关键蛋白的LLPS治疗恶性肿瘤提供理论依据.

Abstract

Liquid-liquid phase separation (LLPS) can drive the spontaneous aggregation of biomacromolecules such as proteins and nucleic acids within cells, forming biomolecular condensate (BMC) with liquid-like properties, also known as membrane-less organelle (MLO). Studies have found that the formation, regulation, and dysregulation of LLPS of key proteins are closely related to processes such as tumor initiation, progression, metastasis, and angiogenesis. This article systematically reviews the mechanism of LLPS and discusses its role at different stages of tumor development, aiming to provide a theoretical basis for treating malignant tumors by targeting the LLPS of key proteins.

关键词

无膜细胞器 / 液-液相分离 / 内在无序区域 / 肿瘤

Key words

membrane-less organelle / liquid-liquid phase separation / intrinsically disordered region / tumor

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基金资助

国家自然科学基金青年基金项目(82303403)

浙江省自然科学基金探索项目(LMS26H160021)