液-液相分离在乳腺癌发生发展中的作用机制及治疗潜力

孙 宇佳1, 奥旭 东*2
1、内蒙古医科大学研究生院
2、北京大学肿瘤医院内蒙古医院，内蒙古恶性肿瘤交叉创新重点实验室

摘要


液-液相分离（liquid-liquid phase separation，LLPS）是生物体系中相分离的核心表现形式，其本质是均一溶液在特定条件下自发分离为浓缩相与稀相并维持动态平衡的过程，可介导生物分子形成无膜凝聚体，调控细胞内多种生理病理活动。大量研究表明，LLPS异常与乳腺癌的发生发展密切相关，其可通过调控染色质架构与转录过程、介导lncRNA与肿瘤相关蛋白的功能异常、参与细胞增殖、迁移、转移、自噬及铁死亡等生理病理过程，以及调控治疗抵抗与细胞凋亡，深刻影响乳腺癌的恶性表型与疾病进展。本文综述了LLPS的基本原理，并重点总结了LLPS在乳腺癌发生发展中的核心调控机制及最新研究进展，探讨了以LLPS为靶点的乳腺癌治疗潜力，为后续LLPS相关基础研究及乳腺癌的临床诊断与治疗提供参考。

关键词


液-液相分离；乳腺癌；肿瘤进展

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参考


[1]Siegel L R, Giaquinto N A, Jemal A.Cancer statistics, 2024[J]. CA: a cancer journal for clinicians, 2024, 74(1):12-49.

[2]Darling L A, Zaslavsky Y B, Uversky N V.Intrinsic Disorder-Based Emergence in Cellular Biology: Physiological and Pathological Liquid-Liquid Phase Transitions in Cells[J].Polymers, 2019, 11(6):990-990.

[3]Forman-Kay D J, Kriwacki W R, Seydoux G.Phase Seperation[J].Journal of Molecular Biology, 2018, 430(23):4603-4606.

[4]Kozai T, Martinez F J, Kapinos E L, et al. Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier[J].Nature Cell Biology, 2025, 27(12):1-13.

[5]K A C, J D M, M T L, et al. Biomolecular Condensation: A New Phase in Cancer Research[J]. Cancer discovery, 2022, 12(9):OOF1-OF13.

[6]Lu B, Qiu R, Wei J, et al. Phase separation of phospho-HDAC6 drives aberrant chromatin architecture in triple-negative breast cancer[J].Nature Cancer, 2024, (prepublish):1-19.

[7]Xie F, Zhou X, Ran Y, et al. Targeting FOXM1 condensates reduces breast tumour growth and metastasis[J].Nature, 2025, 638(8052):1-10.

[8]YiFan Z, JingYu Z, Hong Y, et al. FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27[J].Biochemical and biophysical research communications, 2015, 456(1):232-237.

[9]Zhang R, Huang Q, Chen Z, et al. Phase-Separation of YAP Mediates AJUBA Super Enhancer Activation to Promote Aberrant Mitosis in Breast Cancer[J]. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025, e09341.

[10]Wang H, Zhao B, Zhang J, et al. N4-Acetylcytidine-Mediated CD2BP2-DT Drives YBX1 Phase Separation to Stabilize CDK1 and Promote Breast Cancer Progression[J]. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025, 12(15):e2411834.

[11]RuiHua L, Tian T, QiWei G, et al. A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling[J]. Cell research, 2021, 31(10):1088-1105.

[12]Xiao F, Fangzhou L, Xiang W, et al. LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation[J]. Science China. Life sciences, 2023, 67(3):488-503.

[13]Zhang M, Liang C, Chen T, et al. Phase Separation of PHLDB2 Drives EMT and Tumor Progression in Triple-Negative Breast Cancer[J]. Cancer medicine, 2025, 14(23):e71308.

[14]Fei Y, Chunmiao C, Banzhan R, et al. Regulation of RB1CC1/FIP200 stability and autophagy function by CREBBP-mediated acetylation in an intrinsically disordered region[J]. Autophagy, 2022, 19(6):1662-1677.

[15]Peigang L, Jiaqi Z, Yuchen W, et al. An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration[J]. EMBO reports, 2023, 24(11):e56850-e56850.

[16]Lee J J, Kim H, Park H, et al. Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres[J]. Nucleic acids research, 2024.

[17]Chen X, Gao M, Xia Y, et al. Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates[J].Acta Pharmaceutica Sinica B, 2024, 14(3):1204-1221.

[18]Yang O Y, Ma D, Lin J C, et al. Landscape of gene fusions in hormone receptor-positive breast cancer reveals ADK fusions as drivers of progression and potential therapeutic targets[J].Cell Discovery, 2025, 11(1):89-89.


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