Communications Biology最新文献_第10页

Neutrophil extracellular trap gene expression signatures identify prognostic and targetable signaling axes for inhibiting pancreatic tumour metastasis. 中性粒细胞胞外陷阱基因表达特征确定预后和靶向信号轴抑制胰腺肿瘤转移。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08440-x

Paul C McDonald, James T Topham, Shannon Awrey, Hossein Tavakoli, Rebekah Carroll, Wells S Brown, Zachary J Gerbec, Steve E Kalloger, Joanna M Karasinska, Patricia Tang, Rachel Goodwin, Steven J M Jones, Janessa Laskin, Marco A Marra, Gregg B Morin, Daniel J Renouf, David F Schaeffer, Shoukat Dedhar

{"title":"Neutrophil extracellular trap gene expression signatures identify prognostic and targetable signaling axes for inhibiting pancreatic tumour metastasis.","authors":"Paul C McDonald, James T Topham, Shannon Awrey, Hossein Tavakoli, Rebekah Carroll, Wells S Brown, Zachary J Gerbec, Steve E Kalloger, Joanna M Karasinska, Patricia Tang, Rachel Goodwin, Steven J M Jones, Janessa Laskin, Marco A Marra, Gregg B Morin, Daniel J Renouf, David F Schaeffer, Shoukat Dedhar","doi":"10.1038/s42003-025-08440-x","DOIUrl":"10.1038/s42003-025-08440-x","url":null,"abstract":"Tumour associated neutrophils (TANs) promote metastasis through interactions of Neutrophil Extracellular Traps (NETs) with tumour cells. However, molecular details surrounding the interactions between NETs and Pancreatic Ductal Adenocarcinoma (PDAC) cells are poorly understood. Here, we examine the contribution of NETs in the progression of PDAC, which is characterized by high metastatic propensity. We carry out consensus clustering and pathway enrichment analysis of NET-related genes in an integrated cohort of 369 resectable and metastatic PDAC patient tumour samples, and compile two gene expression signatures comprising of either, integrin-actin cytoskeleton and Epithelial to Mesenchymal Transition (EMT) signaling, or cell death signaling, which identifies patients with very poor to better overall survival, respectively. Tumour Infiltrating neutrophils and NETs associate with ITGB1, CCDC25 and ILK, within clinical and experimental PDAC tumours. Functionally, exposure of PDAC cells to NETs identifies a cytoskeletal dynamic-associated CCDC25-ITGB1-ILK signaling complex which stimulates EMT and migration/invasion. NETosis-driven experimental metastasis to the lungs of PDAC cells delivered through the tail vein of female non-obese diabetic (NOD) scid gamma (NSG) mice is significantly inhibited by ILK knock down. Our data identify novel NET-related gene expression signatures for PDAC patient stratification, and reveal targetable signaling axes to prevent and treat disease progression.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1006"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Visuoaffective day residue in hypnagogia involves sequential bihemispheric interactions between cortical, subcortical, and cerebellar structures. 临睡状态下的视觉情感日残涉及皮层、皮层下和小脑结构之间的连续双脑相互作用。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08429-6

George Vagner Souza, Natália Bezerra Mota, Allan Kardec Barros, Sidarta Ribeiro

{"title":"Visuoaffective day residue in hypnagogia involves sequential bihemispheric interactions between cortical, subcortical, and cerebellar structures.","authors":"George Vagner Souza, Natália Bezerra Mota, Allan Kardec Barros, Sidarta Ribeiro","doi":"10.1038/s42003-025-08429-6","DOIUrl":"10.1038/s42003-025-08429-6","url":null,"abstract":"The intricate interplay between visual perception and emotion determines how waking experience influences mentation through a 'day residue' at once conspicuous yet hard to predict. Here we set out to map the neural sources associated with the visuo-affective processing of the 'day residue' during hypnagogic sleep. To this end, we assessed 28 healthy participants on a combined nap protocol with serial awakenings, pre-sleep stimulation with affective visual images, yoked measures of the semantic similarity between image and imagery reports, affect ratings, estimation of 64-channel EEG sources, and functional connectivity analysis. Overall, low-frequency EEG power was associated with weaker residues, and high-frequency EEG power was associated with stronger residues. The source networks most significantly correlated with imagetic and affective residues were markedly different across wake-sleep states, partially overlapping with the default mode network during N1 for up to 50% and 61%, respectively. The results allowed us to identify neural correlates of the visuo-affective processing of the day's residue, showing that the hypnagogic processing of the waking experience involves complex, dynamic and sequential bi-hemispheric interactions among multiple cortical, subcortical, and cerebellar structures with visual, limbic, optokinetic, and cognitive functions.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"997"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bidirectional information flow in cooperative learning reflects emergent leadership. 合作学习中的双向信息流体现了应急领导。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08445-6

Yuanyuan Li, Ya-Jie Wang, Chang Su, Fang Deng, Yafeng Pan

{"title":"Bidirectional information flow in cooperative learning reflects emergent leadership.","authors":"Yuanyuan Li, Ya-Jie Wang, Chang Su, Fang Deng, Yafeng Pan","doi":"10.1038/s42003-025-08445-6","DOIUrl":"10.1038/s42003-025-08445-6","url":null,"abstract":"Advances in social neuroscience have shown that one of the fundamental characteristics of cooperative learning is synchronization between learners' brains. However, the directionality of this synchronization, and the role of emergent leadership (i.e., a group leader emerges naturally), in cooperative learning remain unclear. Here, we investigated the directionality and dynamics of information flow by leveraging functional near-infrared spectroscopy (fNIRS) hyperscanning and Granger causality analysis (GCA). Through a 6 min dyadic cooperative learning task, we observed that dyads' utterance score increased over time and remained stable at the end of interaction, suggesting successful cooperative learning. At the neural level, we found a stronger leader-to-follower Granger causality in the left middle temporal gyrus, alongside a more pronounced follower-to-leader causality in the left sensorimotor cortex. Moreover, we found that information transfer in both directions increased and peaked around the first half of time into the task, followed by a decline. These temporally similar yet spatially dissociable patterns of directional information flow suggest a hierarchical organization of bidirectional communication during cooperative learning with emergent leadership.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1000"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3BTRON: A Blood-Brain Barrier Recognition Network. 血脑屏障识别网络。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08453-6

Nan Fletcher-Lloyd, Isabel Bravo-Ferrer, Katrine Gaasdal-Bech, Blanca Díaz Castro, Payam Barnaghi

{"title":"3BTRON: A Blood-Brain Barrier Recognition Network.","authors":"Nan Fletcher-Lloyd, Isabel Bravo-Ferrer, Katrine Gaasdal-Bech, Blanca Díaz Castro, Payam Barnaghi","doi":"10.1038/s42003-025-08453-6","DOIUrl":"10.1038/s42003-025-08453-6","url":null,"abstract":"The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis. During ageing, the BBB undergoes structural alterations. Electron microscopy (EM) is the gold standard for studying the structural alterations of the brain vasculature. However, analysis of EM images is time-intensive and can be prone to selection bias, limiting our understanding of the structural effect of ageing on the BBB. Here, we introduce 3BTRON, a deep learning framework for the automated analysis of electron microscopy images of the BBB. Using age as a readout, we trained and validated our model on a unique dataset (n = 359). We show that the proposed model could confidently identify the BBB of aged mouse brains from young mouse brains across three different brain regions, achieving a sensitivity of 77.8% and specificity of 80.0% post-stratification when predicting on unseen data. Additionally, feature importance methods revealed the spatial features of each image that contributed most to the predictions. These findings demonstrate a new data-driven approach to analysing age-related changes in the architecture of the BBB.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1001"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TopBP1 coordinates DNA repair synthesis in mitosis via recruitment of the nuclease scaffold SLX4. TopBP1通过募集核酸酶支架SLX4来协调有丝分裂过程中的DNA修复合成。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08442-9

Jonas Bagge, Kamilla Vandsø Petersen, Sinem N Karakus, Thorbjørn M Nielsen, Johanne Rask, Christian R Brøgger, Jonas Jensen, Meliti Skouteri, Antony M Carr, Ivo A Hendriks, Vibe H Oestergaard, Michael Lisby

{"title":"TopBP1 coordinates DNA repair synthesis in mitosis via recruitment of the nuclease scaffold SLX4.","authors":"Jonas Bagge, Kamilla Vandsø Petersen, Sinem N Karakus, Thorbjørn M Nielsen, Johanne Rask, Christian R Brøgger, Jonas Jensen, Meliti Skouteri, Antony M Carr, Ivo A Hendriks, Vibe H Oestergaard, Michael Lisby","doi":"10.1038/s42003-025-08442-9","DOIUrl":"10.1038/s42003-025-08442-9","url":null,"abstract":"The majority of cancer cells experience replication stress, which ultimately causes them to enter mitosis with underreplicated DNA. To alleviate the consequences of replication stress, cells utilize a mechanism known as MiDAS that functions to complete synthesis of underreplicated DNA in early mitosis. This process is considered an Achilles heel for highly replicative cancers. In this study, we show that human TopBP1 localizes to sites of underreplicated DNA marked by FANCD2 and promotes MiDAS through recruitment of the nuclease scaffold protein SLX4. Additionally, we demonstrate that the recruitment of SLX4 to TopBP1 foci in mitosis depends on TopBP1-K704, SLX4-T1260, and several SUMO-interaction motifs in SLX4. Lastly, we show that the recruitment of SLX4 to TopBP1 foci in mitosis is important to prevent transmission of DNA damage to daughter cells. Based on this, we hypothesize that targeting the TopBP1-SLX4 interaction in mitosis may be a potential strategy for anti-cancer therapy.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1005"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying late Pleistocene and Holocene refugia for baboons. 狒狒晚更新世和全新世避难所的鉴定。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-04 DOI: 10.1038/s42003-025-08419-8

James Blinkhorn, Dietmar Zinner, Lucy Timbrell, Andrea Manica, Matt Grove, Eleanor M L Scerri

{"title":"Identifying late Pleistocene and Holocene refugia for baboons.","authors":"James Blinkhorn, Dietmar Zinner, Lucy Timbrell, Andrea Manica, Matt Grove, Eleanor M L Scerri","doi":"10.1038/s42003-025-08419-8","DOIUrl":"10.1038/s42003-025-08419-8","url":null,"abstract":"Climate change has the scope to significantly modulate the distribution of floral and faunal taxa, with those regions persistently suitable to a population through the largest environmental perturbations termed \"refugia\". Within Africa, focus has been placed on forest refugia during glacial cycles as hotspots of biodiversity, whilst refugia for savannah species have been overlooked. We compiled a comprehensive dataset of baboon occurrences and fitted species distribution model ensembles to predict the present potential habitable range of each species and the genus as a whole. We then hindcasted these models to palaeoclimate reconstructions spanning the Late Pleistocene and Holocene in 1-thousand-year time steps to predict potentially habitable ranges throughout a full interglacial-glacial cycle. Our results indicate a substantial mosaic of refugia in the eastern African Rift Valley system, a discrete refugium in southern and south-western Africa, as well as isolated refugia across western Africa and Arabia. Orbital precession and obliquity both play a role in driving maxima and minima or predicted habitable ranges for alternate baboon species, but these appear expressed within ca. 100 thousand-year eccentricity cycles. This supports the use of full interglacial-glacial cycles, rather than simply comparing peak glacial and interglacial conditions, to determine the presence of refugia.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1003"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploratory GABAa-informed control network modulates hyperarousal brain dynamics in chronic insomnia. 探索性gabaa控制网络调节慢性失眠症的高唤醒脑动力学。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-03 DOI: 10.1038/s42003-025-08439-4

Liyong Yu, Liang Gong, Xiaoqin Chen, Yuqi He, Rong Li, Xiaojuan Hong, Qi Zhang, Siyi Yu

{"title":"Exploratory GABAa-informed control network modulates hyperarousal brain dynamics in chronic insomnia.","authors":"Liyong Yu, Liang Gong, Xiaoqin Chen, Yuqi He, Rong Li, Xiaojuan Hong, Qi Zhang, Siyi Yu","doi":"10.1038/s42003-025-08439-4","DOIUrl":"10.1038/s42003-025-08439-4","url":null,"abstract":"Chronic insomnia disorder is characterized by hyperarousal, a heightened cortical activation pattern that disrupts normal sleep. While hyperarousal has been linked to altered brain state dynamics, the underlying neurobiological mechanisms remain poorly understood, particularly regarding the influence of inhibitory neurotransmitter signaling through GABAa receptors. This study demonstrates that hyperarousal in chronic insomnia is characterized by more frequent and unpredictable transitions between brain states compared to healthy controls, as revealed by hidden Markov modeling of resting-state functional MRI data. By conducting an exploratory integration of DTI-based structural connectivity and regional GABAa receptor distribution within a network control theory framework, we find that chronic insomnia is associated with a flattened energy landscape reflecting hyperarousal, indicating that less energy is required for the brain to transition between states. Notably, accounting for GABAa receptor distribution increases the control energy required for state transitions and is associated with greater stability in brain state dynamics. These findings provide neurobiological insights into hyperarousal in chronic insomnia, with an exploratory analysis suggesting a modulatory role of GABAergic signaling in shaping the brain's dynamic dysfunction.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"991"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolution of iGluR ligand specificity, polyamine regulation, and ion selectivity inferred from a placozoan epsilon receptor. 从placozoan epsilon受体推断的iGluR配体特异性、多胺调节和离子选择性的进化。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-03 DOI: 10.1038/s42003-025-08402-3

Anhadvir Singh, Boris S Zhorov, Luis A Yanez-Guerra, Alessandra Aleotti, Chloe C Koens, C Defne Yanartas, Yunqi Song, Federico Javier Miguez Cabello, Derek Bowie, Adriano Senatore

{"title":"Evolution of iGluR ligand specificity, polyamine regulation, and ion selectivity inferred from a placozoan epsilon receptor.","authors":"Anhadvir Singh, Boris S Zhorov, Luis A Yanez-Guerra, Alessandra Aleotti, Chloe C Koens, C Defne Yanartas, Yunqi Song, Federico Javier Miguez Cabello, Derek Bowie, Adriano Senatore","doi":"10.1038/s42003-025-08402-3","DOIUrl":"10.1038/s42003-025-08402-3","url":null,"abstract":"Epsilon ionotropic glutamate receptors (iGluRs) are a recently defined clade of neurotransmitter receptors that are found in all major metazoan lineages that are distinct from α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, delta, phi (i.e., AKDF) and N-methyl-D-aspartate NMDA receptors. Here, we explore the evolution of iGluRs by generating a broad species-guided phylogeny of eukaryotic iGluRs and a comprehensive phylogeny of placozoan receptors, uncovering marked diversification of epsilon type receptors within Placozoa. Functional characterization of one epsilon receptor from the placozoan species Trichoplax adhaerens, named GluE1αA, reveals sensitivity to glycine, alanine, serine, and valine, but not glutamate. We demonstrate that changing just three amino acids in the ligand binding domain could convert ligand specificity of GluE1αA from glycine to glutamate, also causing nascent sensitivity to AMPA and increased sensitivity to the blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). We also demonstrate that an atypical serine in the pore Q/R/N site confers diminished Ca2+ permeation and sensitivity to polyamine block, imposing similar effects on the human GluA2 receptor, and that a conserved aspartate four amino acids downstream of the Q/R/N site is crucial for polyamine regulation. Thus, key molecular determinants for polyamine regulation are conserved between AKDF and epsilon receptors.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"994"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Species loss in key habitats accelerates regional food web disruption. 主要栖息地的物种丧失加速了区域食物网的破坏。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-03 DOI: 10.1038/s42003-025-08396-y

Merin Reji Chacko, Camille Albouy, Florian Altermatt, Victor Boussange, Martin Brändle, Nina Farwig, Martin M Gossner, Hsi-Cheng Ho, Alain Joss, Felix Neff, Loïc Pellissier

{"title":"Species loss in key habitats accelerates regional food web disruption.","authors":"Merin Reji Chacko, Camille Albouy, Florian Altermatt, Victor Boussange, Martin Brändle, Nina Farwig, Martin M Gossner, Hsi-Cheng Ho, Alain Joss, Felix Neff, Loïc Pellissier","doi":"10.1038/s42003-025-08396-y","DOIUrl":"10.1038/s42003-025-08396-y","url":null,"abstract":"Understanding the robustness of ecological networks against sustained species losses is paramount to devising effective biodiversity conservation strategies. To explore the impacts of species losses on network robustness (the capacity of food webs to withstand primary extinctions), we used a trophic metaweb of 7808 vertebrates, invertebrates and plants and 281,023 interactions across Switzerland. We inferred twelve regional multi-habitat food webs and simulated non-random species extinction scenarios on these webs, focusing on broad habitat types and regional species abundances. Here, we show that targeted removal of species associated with specific habitat types, particularly wetlands, resulted in greater network fragmentation and accelerated network collapse compared to random species removals. Networks were more vulnerable to the initial loss of common rather than rare species. These findings underscore the critical need for integrated conservation strategies maintaining a diverse mosaic of habitats in a landscape to mitigate the cascading effects of species loss.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"988"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer cell type-specific derepression of transposable elements by inhibition of chromatin modifier enzymes. 通过抑制染色质修饰酶对癌细胞类型特异性转座因子的抑制。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-03 DOI: 10.1038/s42003-025-08413-0

Divyesh Patel, Ville Tiusanen, Konsta Karttunen, Päivi Pihlajamaa, Biswajyoti Sahu

{"title":"Cancer cell type-specific derepression of transposable elements by inhibition of chromatin modifier enzymes.","authors":"Divyesh Patel, Ville Tiusanen, Konsta Karttunen, Päivi Pihlajamaa, Biswajyoti Sahu","doi":"10.1038/s42003-025-08413-0","DOIUrl":"10.1038/s42003-025-08413-0","url":null,"abstract":"Derepression of transposable elements (TE) by epigenetic therapy leads to the activation of immune response in cancer cells. However, the molecular mechanism of TE regulation by distinct chromatin modifier enzymes (CME) in context of p53 is still elusive. Here, we used FDA-approved epigenetic drugs to systematically inhibit distinct CMEs in p53 wild-type and p53-mutant colorectal, esophageal, and prostate cancer cells. We show that distinct TE subfamilies are derepressed by inhibition of different CMEs in cell type-specific manner. Co-inhibition of DNMT and HDAC (DNMTi-HDACi) had the most consistent effect across cancer types. Loss of p53 results in stronger TE activation and TE-chimeric transcript expression and this effect is largely mediated by the non-genomic actions of p53. Robust immune response elicited by DNMTi-HDACi is due to induced inverted repeat Alu expression concomitant with reduced ADAR1-mediated Alu RNA editing. Collectively, our systematic analyses provide insights for rational use of epigenetic therapies in distinct cancers.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"992"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0