Liquid–liquid phase separation in hepatocellular carcinoma

Liquid-liquid phase separation (LLPS) drives the formation of membraneless intracellular compartments within both cytoplasm and nucleus. These compartments can form distinct physicochemical environments, and in particular display different concentrations of proteins, RNA, and macromolecules compared...

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Main Authors: Jianguo Xu, Wangwang Liu, Yihan Yao, Tuomas P. J. Knowles, Zhi-Gang Zhang, Yan-Li Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2024.1454587/full
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author Jianguo Xu
Wangwang Liu
Yihan Yao
Tuomas P. J. Knowles
Zhi-Gang Zhang
Yan-Li Zhang
author_facet Jianguo Xu
Wangwang Liu
Yihan Yao
Tuomas P. J. Knowles
Zhi-Gang Zhang
Yan-Li Zhang
author_sort Jianguo Xu
collection DOAJ
description Liquid-liquid phase separation (LLPS) drives the formation of membraneless intracellular compartments within both cytoplasm and nucleus. These compartments can form distinct physicochemical environments, and in particular display different concentrations of proteins, RNA, and macromolecules compared to the surrounding cytosol. Recent studies have highlighted the significant role of aberrant LLPS in cancer development and progression, impacting many core processes such as oncogenic signalling pathways, transcriptional dysregulation, and genome instability. In hepatocellular carcinoma (HCC), aberrant formation of biomolecular condensates has been observed in a number of preclinical models, highlighting their significance as an emerging factor in understanding cancer biology and its molecular underpinnings. In this review, we summarize emerging evidence and recent advances in understanding the role of LLPS in HCC, with a particular focus on the regulation and dysregulation of cytoplasmic and nuclear condensates in cancer cells. We finally discuss how an emerging understanding of phase separation processes in HCC opens up new potential treatment avenues.
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publishDate 2024-12-01
publisher Frontiers Media S.A.
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series Frontiers in Cell and Developmental Biology
spelling doaj-art-0f672bb5f41a4eedb0f3ae66a0bcd9402025-08-20T02:00:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-12-011210.3389/fcell.2024.14545871454587Liquid–liquid phase separation in hepatocellular carcinomaJianguo Xu0Wangwang Liu1Yihan Yao2Tuomas P. J. Knowles3Zhi-Gang Zhang4Yan-Li Zhang5State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United KingdomYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United KingdomState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaLiquid-liquid phase separation (LLPS) drives the formation of membraneless intracellular compartments within both cytoplasm and nucleus. These compartments can form distinct physicochemical environments, and in particular display different concentrations of proteins, RNA, and macromolecules compared to the surrounding cytosol. Recent studies have highlighted the significant role of aberrant LLPS in cancer development and progression, impacting many core processes such as oncogenic signalling pathways, transcriptional dysregulation, and genome instability. In hepatocellular carcinoma (HCC), aberrant formation of biomolecular condensates has been observed in a number of preclinical models, highlighting their significance as an emerging factor in understanding cancer biology and its molecular underpinnings. In this review, we summarize emerging evidence and recent advances in understanding the role of LLPS in HCC, with a particular focus on the regulation and dysregulation of cytoplasmic and nuclear condensates in cancer cells. We finally discuss how an emerging understanding of phase separation processes in HCC opens up new potential treatment avenues.https://www.frontiersin.org/articles/10.3389/fcell.2024.1454587/fullliquid-liquid phase separationhepatocellular carcinomacytoplasmic condensatesnuclear condensatesdroplets
spellingShingle Jianguo Xu
Wangwang Liu
Yihan Yao
Tuomas P. J. Knowles
Zhi-Gang Zhang
Yan-Li Zhang
Liquid–liquid phase separation in hepatocellular carcinoma
Frontiers in Cell and Developmental Biology
liquid-liquid phase separation
hepatocellular carcinoma
cytoplasmic condensates
nuclear condensates
droplets
title Liquid–liquid phase separation in hepatocellular carcinoma
title_full Liquid–liquid phase separation in hepatocellular carcinoma
title_fullStr Liquid–liquid phase separation in hepatocellular carcinoma
title_full_unstemmed Liquid–liquid phase separation in hepatocellular carcinoma
title_short Liquid–liquid phase separation in hepatocellular carcinoma
title_sort liquid liquid phase separation in hepatocellular carcinoma
topic liquid-liquid phase separation
hepatocellular carcinoma
cytoplasmic condensates
nuclear condensates
droplets
url https://www.frontiersin.org/articles/10.3389/fcell.2024.1454587/full
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AT yihanyao liquidliquidphaseseparationinhepatocellularcarcinoma
AT tuomaspjknowles liquidliquidphaseseparationinhepatocellularcarcinoma
AT zhigangzhang liquidliquidphaseseparationinhepatocellularcarcinoma
AT yanlizhang liquidliquidphaseseparationinhepatocellularcarcinoma