The global landscape and research trend of phase separation in cancer: a bibliometric analysis and visualization DOI Creative Commons
Mengzhu Li,

Yi-Zhan Zhang,

Jiajun Zhao

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 2, 2023

Cancer as a deathly disease with high prevalence has impelled researchers to investigate its causative mechanisms in the search for effective therapeutics. Recently, concept of phase separation been introduced biological science and extended cancer research, which helps reveal various pathogenic processes that have not identified before. As process soluble biomolecules condensed into solid-like membraneless structures, is associated multiple oncogenic processes. However, there are no bibliometric characteristics these results. To provide future trends identify new frontiers this field, analysis was conducted study.The Web Science Core Collection (WoSCC) used literature on from 1/1/2009 31/12/2022. After screening literature, statistical visualization were carried out by VOSviewer software (version 1.6.18) Citespace (Version 6.1.R6).A total 264 publications, covering 413 organizations 32 countries, published 137 journals, an increasing trend publication citation numbers per year. The USA China two countries largest number University Chinese Academy Sciences most active institution based articles cooperations. Molecular Cell frequent publisher citations H-index. productive authors Fox AH, De Oliveira GAP, Tompa P. Overlay, whilst few had strong collaboration each other. combined concurrent burst keywords revealed research hotspots related tumor microenvironments, immunotherapy, prognosis, p53, cell death.Phase separation-related remained hot streak period exhibited promising outlook. Although inter-agency existed, cooperation among groups rare, author dominated field at current stage. Investigating interfaced effects between microenvironments carcinoma behaviors, constructing relevant prognoses therapeutics such immune infiltration-based prognosis immunotherapy might be next study cancer.

Language: Английский

Dysregulation of transcriptional condensates in human disease: mechanisms, biological functions, and open questions DOI

Kaeli M. Mathias,

Yiman Liu, Liling Wan

et al.

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 86, P. 102203 - 102203

Published: May 23, 2024

Language: Английский

Citations

4
The role of liquid-liquid phase separation in defining cancer EMT DOI
Yuan Li, Yuqing Feng, Songmei Geng

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 353, P. 122931 - 122931

Published: July 20, 2024

Language: Английский

Citations

4
Biomolecular condensates and disease pathogenesis DOI
Ke Ruan, Ge Bai, Yanshan Fang

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: 67(9), P. 1792 - 1832

Published: July 17, 2024

Language: Английский

Citations

4
Versatile roles of disordered transcription factor effector domains in transcriptional regulation DOI Creative Commons
Rhea R. Datta,

Dilan Akdogan,

Elif B. Tezcan

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Transcription, a crucial step in the regulation of gene expression, is tightly controlled and involves several essential processes, such as chromatin organization, recognition specific genomic sequences, DNA binding, ultimately recruiting transcriptional machinery to facilitate transcript synthesis. At center this are transcription factors (TFs), which comprise at least one DNA-binding domain (DBD) an effector (ED). Although structure function DBDs have been well studied, our knowledge domains limited. EDs particular importance generating distinct responses between protein members same TF family that similar specificities. The study activity conferred by has traditionally conducted through examining protein-protein interactions. However, recent research uncovered alternative mechanisms regulate formation condensates increase local concentration factors, cofactors, coregulated genes, binding. Here, we provide comprehensive overview known roles factor EDs, with focus on disordered regions. Additionally, emphasize significance intrinsically regions (IDRs) during regulation. We examine underlying establishment maintenance specificity structural properties predominantly EDs. then current understanding these domains, including their physical chemical characteristics, functional roles.

Language: Английский

Citations

0
Liquid–liquid phase separation in diseases DOI Creative Commons
Xinyue Zhang, Yuan Lin, Wanlu Zhang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(7)

Published: July 1, 2024

Liquid-liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules P-bodies, containing RNA protein. RNA-RNA RNA-protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent external factors, support protein-RNA interaction networks form condensates involved variety diseases, particularly neurodegenerative diseases cancer. Modulating phenomenon multiple pathogenic proteins for treatment cancer could present promising direction, though recent advances this area are limited. Here, we summarize detail complexity constructing signaling pathways highlight cancers. We also explore modifications on alter progression because these influence certain or formation granules, discuss possibility proper manipulation process restore cellular homeostasis develop therapeutic drugs eradication diseases. This review attempts potential opportunities by elaborating connection between LLPS, modification, their roles

Language: Английский

Citations

3
Phase Separation: A New Dimension to Understanding Tumor Biology and Therapy DOI Creative Commons
Xingwen Wang,

Minqiao Lu,

Yi Zhang

et al.

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(2)

Published: May 5, 2025

ABSTRACT Liquid–liquid phase separation (LLPS) plays a critical role in orchestrating various cellular processes, such as gene expression, signal transduction, and protein synthesis, by compartmentalizing components without membrane boundaries. Emerging research has illuminated how dysregulated LLPS is integral to cancer development influencing tumorigenesis, metastasis, immune system evasion, resistance therapy. The subtle differences are crucial for understanding progression finding new treatments. However, despite its significant implications oncology, the potential of specifically targeting therapy not been thoroughly investigated. This review delves into mechanisms LLPS, exploring physiological triggers their consequences biology. We discuss profound impact on hallmarks outline innovative strategies aimed at LLPS. These include direct inhibition condensate formation modulation related signaling pathways. Although poses several challenges, specificity delivery methods, it represents promising frontier treatment, potentially revolutionizing we approach emphasizes academic therapeutic importance advocating an exciting valuable target future treatment strategies.

Language: Английский

Citations

0
The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm? DOI
Shwetha Sreenivasan,

Paul Heffren,

Kyung‐Shin Suh

et al.

Protein Science, Journal Year: 2023, Volume and Issue: 33(2)

Published: Dec. 11, 2023

During protein evolution, some amino acid substitutions modulate function ("tuneability"). In most proteins, the tuneable range is wide and can be sampled by a set of variants that each contains multiple substitutions. other full accessed single substitution. Indeed, in globular site-saturating at an individual "rheostat" position. However, proteins with intrinsically disordered regions (IDRs), functional studies-which would also detect tuneability-used or small deletions. transcriptional activation domains (ADs), studies led to "acidic exposure" model, which does not anticipate existence rheostat positions. few did assess effects on AD function, results were mixed: ADs two full-length transcription factors show tuneability, whereas fragment third was this study, we tested tuneability human class II transactivator (CIITA). Sequence analyses experiments showed CIITA's IDR. Functional assays singly-substituted highly tuneable, outcomes predicted acidic exposure model. Four positions behavior for activation. Thus, different IDRs vary widely. Future are needed illuminate biophysical features govern whether IDR

Language: Английский

Citations

8
Phase separation in DNA damage response: New insights into cancer development and therapy DOI Creative Commons

Lingwei Li,

Litong Yao, Mozhi Wang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189206 - 189206

Published: Nov. 1, 2024

Language: Английский

Citations

1
Whole genome profiling of rare pediatric thoracic tumors elucidates a YAP1::LEUTX fusion in an unclassified biphasic embryonal neoplasm DOI

Georgi Lukose,

Majd Al Assaad,

Jordan H. Driskill

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 264, P. 155726 - 155726

Published: Nov. 19, 2024

Language: Английский

Citations

1
Phase separation of PML/RARα and BRD4 coassembled microspeckles governs transcriptional dysregulation in acute promyelocytic leukemia DOI Creative Commons
Yi Zhang, Jiacheng Lou, Yabin Liu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(34)

Published: Aug. 13, 2024

In acute promyelocytic leukemia (APL), the leukemia-retinoic acid receptor alpha (PML/RARα) fusion protein destroys PML nuclear bodies (NBs), leading to formation of microspeckles. However, our understanding, largely learned from morphological observations, lacks insight into mechanisms behind PML/RARα-mediated microspeckle and its role in APL leukemogenesis. This study presents evidence uncovering liquid–liquid phase separation (LLPS) as a key mechanism process is facilitated by intrinsically disordered region containing large portion smaller segment RARα. We demonstrate coassembly bromodomain-containing 4 (BRD4) within condensates, differing wild-type PML-formed NBs. absence PML/RARα, NBs BRD4 puncta exist two independent phases, but presence PML/RARα disrupts redistributes distinct phase, forming PML/RARα-assembled Genome-wide profiling reveals PML/RARα-induced redistribution across genome, with preferential binding super-enhancers broad-promoters (SEBPs). Mechanistically, recruited facilitating chromatin exert transcriptional activation essential for survival. Perturbing LLPS through chemical inhibition (1, 6-hexanediol) significantly reduces co-occupancy BRD4, attenuating their target gene activation. Finally, series experimental validations primary patient samples confirm that forms microspeckles recruits coassemble co-occupies SEBP regions. Our findings elucidate biophysical, pathological, dynamics microspeckles, underscoring importance mediating enables initiate APL.

Language: Английский

Citations

1