Liquid‒liquid phase separation: roles and implications in future cancer treatment

Liu, Zheran; Qin, Zijian; Liu, Yingtong; Xia, Xi; He, Lijun; Chen, Na; Hu, Xiaolin; Peng, Xingchen

doi:10.7150/ijbs.81521

Cited by 12 publications

(2 citation statements)

References 150 publications

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“…More and more studies are now showing that liquid–liquid phase separation for targeting tumours is an important anticancer therapeutic strategy. Therefore, exploring the mechanism and function of liquid–liquid phase separation will provide some important insights for future cancer therapy 18–20 . In this study, we constructed LLPSI based on five liquid–liquid phase separation genes (MAPT, WDR62, PLK1, CDCA8 and TOP2A).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, exploring the mechanism and function of liquid–liquid phase separation will provide some important insights for future cancer therapy. 18 , 19 , 20 In this study, we constructed LLPSI based on five liquid–liquid phase separation genes (MAPT, WDR62, PLK1, CDCA8 and TOP2A). We found that LLPSI can be used as a marker for HCC staging and can effectively predict the prognosis and immunotherapy outcome of HCC patients, which was validated by external datasets.…”

Section: Discussionmentioning

confidence: 99%

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The liquid–liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma

Wang,

Zhao

et al. 2024

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) is a common and fatal malignancy characterized by poor patient prognosis and treatment outcome. The process of liquid–liquid phase separation in tumour cells alters the dysfunction of biomolecular condensation in tumour cells, which affects tumour progression and treatment. We downloaded the data of HCC samples from TCGA database and GEO database, and used a machine learning method to build a new liquid–liquid phase separation index (LLPSI) by liquid–liquid phase separation related genes. The LLPSI‐related column line Figure was constructed to provide a quantitative tool for clinical practice. HCC patients were divided into high and low LLPSI groups based on LLPSI, and clinical features, tumour immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analysed. LLPSI, which consists of five liquid–liquid phase separation‐associated genes (MAPT, WDR62, PLK1, CDCA8 and TOP2A), is a reliable predictor of survival in patients with HCC and has been validated in multiple external datasets. We found that the high LLPSI group showed higher levels of immune cell infiltration and better response to immunotherapy compared to the low LLPSI group, and LLPSI can also be used for prognostic prediction in various cancers other than HCC. In vitro experiments verified that knockdown of MAPT could inhibit the proliferation and migration of HCC. The LLPSI identified in this study can accurately assess the prognosis of patients with HCC and identify patient populations that will benefit from immunotherapy, providing valuable insights into the clinical management of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The liquid–liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma

Wang,

Zhao

et al. 2024

J Cellular Molecular Medi

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Unveiling the Complexity of cis‐Regulation Mechanisms in Kinases: A Comprehensive Analysis

Navarro,

Alonso,

Martínez‐Pérez

et al. 2024

Proteins

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Protein cis‐regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP‐binding sites, post‐translational modifications, and disease‐associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

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Liquid-liquid phase separation in aging: Novel insights in the pathogenesis and therapeutics

Wang,

Tang,

Yan

et al. 2024

Ageing Research Reviews

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Liquid‒liquid phase separation: roles and implications in future cancer treatment

Cited by 12 publications

References 150 publications

The liquid–liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma

The liquid–liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma

Unveiling the Complexity of cis‐Regulation Mechanisms in Kinases: A Comprehensive Analysis

Liquid-liquid phase separation in aging: Novel insights in the pathogenesis and therapeutics

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