The hallmarks of cancer immune evasion

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

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Regulation of cGAS–STING signalling and its diversity of cellular outcomes

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

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A novel biosensor for the spatiotemporal analysis of STING activation during innate immune responses to dsDNA

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

The cGAS-STING signalling pathway has a central role in the innate immune response to extrinsic and intrinsic sources of cytoplasmic dsDNA. At core this is cGAS-dependent production intra- extra-cellular messenger cGAMP, which activates STING leads IRF3-dependent expression cytokines interferons. Despite its relevance viral bacterial infections, cell death, genome instability, lack specific live-cell reporters precluded spatiotemporal analyses signalling. Here, we generate fluorescent biosensor termed SIRF (STING-IRF3), reports on functional interaction between activated IRF3 at Golgi. We show that cells harbouring react time- concentration-dependent manner both agonists microenvironmental cGAMP. demonstrate new suitable for single-cell characterisation responses HSV-1 infection, mtDNA release upon apoptosis, or other Furthermore, our results indicate not by ruptured micronuclei, suggesting cytosolic pattern recognition receptors underlie interferon chromosomal instability.

Language: Английский

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Nuclear and genome dynamics underlying DNA double-strand break repair

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Mitotic lethality prevents inflammation

Nature Cell Biology, Journal Year: 2025, Volume and Issue: 27(1), P. 7 - 8

Published: Jan. 1, 2025

Language: Английский

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Recent Mechanistic Insight into the Immunogenic Properties of Radiation-Induced Micronuclei

International Journal of Radiation Oncology*Biology*Physics, Journal Year: 2025, Volume and Issue: 121(2), P. 283 - 286

Published: Jan. 15, 2025

Language: Английский

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Chromosome number alterations cause apoptosis and cellular hypertrophy in induced pluripotent stem cell models of embryonic epiblast cells

Biology Open, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 15, 2025

ABSTRACT Chromosomal aneuploidies are a major cause of developmental failure and pregnancy loss. To investigate the possible consequences aneuploidy on early embryonic development in vitro, we focused primed pluripotent stem cells that relatable to epiblast post-implantation embryos vivo. We used human induced (iPSCs) as an model altered chromosome numbers by treating with reversine, small-molecule inhibitor monopolar spindle 1 kinase (MSP1) inactivates assembly checkpoint, which has been strongly implicated mis-segregation generation. Upon reversine treatment, obtained varied chromosomal content retained pluripotency potential differentiate into three germ lineages. However, these displayed lagging chromosomes, increased micronuclei content, high p53 expression excessive apoptotic activity. Cell proliferation was not affected. Prolonged vitro culture resulted selective pool supernumerary exhibited cellular hypertrophy, enlarged nuclei, overproduction total RNAs proteins. conclude DNA damage responses, apoptosis, improper mass functions mechanisms contribute abnormal development.

Language: Английский

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Progress in extracellular vesicle@STING towards immune regulation

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110990 - 110990

Published: Feb. 1, 2025

Language: Английский

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Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers

Biology of the Cell, Journal Year: 2025, Volume and Issue: 117(2)

Published: Feb. 1, 2025

ABSTRACT Background Information Mitosis is crucial for the faithful transmission of genetic material, and disruptions can result in chromosomal instability (CIN), a hallmark cancer. CIN known driver tumor heterogeneity anti‐cancer drug resistance, thus highlighting need to assess levels cancer cells design effective targeted therapy. While micronuclei are widely recognized as markers, we have recently identified toroidal nucleus, novel ring‐shaped nuclear phenotype arising well from chromosome mis‐segregation. Results Here, examined whether increasing envelope stiffness through lamin A/C overexpression could affect formation nuclei micronuclei. Interestingly, led an increase while reducing prevalence. We demonstrated that chromatin compaction drive nuclei. Furthermore, inhibition autophagy lysosomal function elevated frequency without affecting number whole cell population. this divergence between two biomarkers independent defects A processing. Conclusions Significance These findings uncover complex interplay architecture CIN, advancing our understanding mechanisms supporting genomic stability further contributing biology.

Language: Английский

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Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers

Cancer Discovery, Journal Year: 2025, Volume and Issue: 15(3), P. 461 - 480

Published: March 3, 2025

Abstract Thirty years ago, the cloning of first breast cancer susceptibility gene, BRCA1, marked a milestone in our understanding hereditary and ovarian cancers. This discovery initiated extensive research into DNA repair mechanisms, BRCA1-associated tumorigenesis, therapeutic interventions. Despite these advances, critical questions remain unanswered, such as evolution tumors their tissue specificity. These issues hinder development effective treatment prevention strategies, which ultimately aim to improve quality life for BRCA1 mutation carriers. In this review, we discuss current knowledge, identify existing gaps, suggest possible avenues tackle challenges. Significance: Here, explore impact three decades on lives carriers propose strategies cancer.

Language: Английский

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