EMBO Journal最新文献

Single-molecule imaging of transcription dynamics, RNA localization and fate in human T cells. 人T细胞转录动力学、RNA定位和命运的单分子成像。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-14 DOI: 10.1038/s44318-025-00592-0

M Valeria Lattanzio, Nikolina Šoštarić, Nandhini Kanagasabesan, Branka Popović, Antonia Bradarić, Leyma Wardak, Aurélie Guislain, Philipp Savakis, Evelina Tutucci, Monika C Wolkers

{"title":"Single-molecule imaging of transcription dynamics, RNA localization and fate in human T cells.","authors":"M Valeria Lattanzio, Nikolina Šoštarić, Nandhini Kanagasabesan, Branka Popović, Antonia Bradarić, Leyma Wardak, Aurélie Guislain, Philipp Savakis, Evelina Tutucci, Monika C Wolkers","doi":"10.1038/s44318-025-00592-0","DOIUrl":"https://doi.org/10.1038/s44318-025-00592-0","url":null,"abstract":"T cells are critical effector cells counteracting infections and malignancies. To achieve this, they produce pro-inflammatory cytokines, including IFN-γ and TNF. Cytokine production is a tightly regulated process, but the relative contribution of transcriptional and post-transcriptional regulation to mRNA expression remains unknown. We optimized single-molecule FISH for primary human T cells (T-cell smFISH) to simultaneously quantify nascent RNA, levels of mature mRNA, and its localization with single-cell resolution. T-cell smFISH uncovered heterogeneous cytokine mRNA levels, with high cytokine producers displaying biallelic IFNG/TNF RNA transcription activity. Throughout activation, nuclear cytokine mRNAs accumulated, whereas cytoplasmic cytokine mRNA was degraded through translation-dependent decay. Lastly, T-cell smFISH uncovered cytokine-specific regulation by the RNA-binding protein HuR. Thus, T-cell smFISH provides novel insights in the intricate (post)-transcriptional processes in T cells.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of maternal antibody interference with rotavirus vaccination. 母源抗体干扰轮状病毒疫苗接种的机制。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-14 DOI: 10.1038/s44318-025-00582-2

Tawny L Chandler, Sarah Woodyear, Valerie Chen, Tom M Lonergan, Natalie Baker, Katherine Harcourt, Simon Clare, Faraz Ahmed, Sarah L Caddy

{"title":"Mechanisms of maternal antibody interference with rotavirus vaccination.","authors":"Tawny L Chandler, Sarah Woodyear, Valerie Chen, Tom M Lonergan, Natalie Baker, Katherine Harcourt, Simon Clare, Faraz Ahmed, Sarah L Caddy","doi":"10.1038/s44318-025-00582-2","DOIUrl":"https://doi.org/10.1038/s44318-025-00582-2","url":null,"abstract":"Maternal antibodies are transferred transplacentally to fetuses and then through lactation to infants to protect them whilst their own immune system is still immature. However, these maternal antibodies also suppress neonatal B-cell responses, thereby impairing vaccine efficacy and leaving infants potentially vulnerable to life-threatening pathogens, such as rotaviruses. Currently available rotavirus vaccines are composed of live-attenuated viral strains administered to infants orally at 6-8 weeks old. Although high concentrations of maternal antibodies correlate with poor production of antibodies following vaccination (i.e., seroconversion), the immunological basis of this interference is unknown. To investigate the underlying mechanisms, we here developed a mouse model of neonatal oral rotavirus vaccination, in which vaccination only fails to induce seroconversion if maternal antibodies are present. Such antibodies are shown to block vaccine replication, while faster maternal antibody waning is observed in vaccinated compared to unvaccinated pups. FcγRIIB deletion does not overcome interference in pups, although pup IgG levels increase when maternal antibody titers are very low. Our findings show that maternal antibody-mediated vaccine clearance is a key mechanism of interference with oral rotavirus vaccines, with a minor role for FcγRIIB in neonatal IgG responses.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures. DNA合成的空间映射揭示了人类复制纳米结构的动力学和几何结构。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-07 DOI: 10.1038/s44318-025-00574-2

Michael Hawgood, Bruno Urién, Ana Agostinho, Praghadhesh Thiagarajan, Giovanni Giglio, Yiqiu Yang, Xue Zhang, Gemma Quijada, Matilde Fonseca, Jiri Bartek, Hans Blom, Bennie Lemmens

{"title":"Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures.","authors":"Michael Hawgood, Bruno Urién, Ana Agostinho, Praghadhesh Thiagarajan, Giovanni Giglio, Yiqiu Yang, Xue Zhang, Gemma Quijada, Matilde Fonseca, Jiri Bartek, Hans Blom, Bennie Lemmens","doi":"10.1038/s44318-025-00574-2","DOIUrl":"https://doi.org/10.1038/s44318-025-00574-2","url":null,"abstract":"DNA replication is essential to life and ensures the accurate transmission of genetic information, which is significantly disturbed during cancer development and chemotherapy. While DNA replication is tightly controlled in time and space, methods to visualise and quantify replication dynamics within 3D human cells are lacking. Here, we introduce 3D-Spatial Assay for Replication Kinetics (3D-SPARK), an approach enabling nanoscale analysis of DNA synthesis dynamics in situ. 3D-SPARK integrates optimised nucleotide analogue pulse labelling with super-resolution microscopy to detect, classify, and quantify replication nanostructures in single cells. By combining immunofluorescence techniques with click chemistry-based nascent DNA labelling and transfection of fluorescent nucleotide derivatives, we map multi-colour DNA synthesis events in relation to established replication proteins, local RNA-protein condensates or large subnuclear domains. We demonstrate quantitative changes in size, relative abundance and spatial arrangement of nanoscale DNA synthesis events upon chemotherapeutic treatment, CDC6 oncogene expression and loss of chromatin organiser RIF1. The flexibility, precision and modular design of 3D-SPARK helps bridging the gap between spatial cell biology, genomics, and 2D fibre-based replication studies in health and disease.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mapping cryptic phosphorylation sites in the human proteome. 绘制人类蛋白质组的隐磷酸化位点。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-03 DOI: 10.1038/s44318-025-00567-1

Dino Gasparotto, Annarita Zanon, Valerio Bonaldo, Elisa Marchiori, Massimo Casagranda, Erika Di Domenico, Laura Copat, Tommaso Fortunato Asquini, Marta Rigoli, Sirio Vittorio Feltrin, Nuria Lopez Lorenzo, Graziano Lolli, Maria Pennuto, Jesùs R Requena, Omar Rota Stabelli, Giovanni Minervini, Cristian Micheletti, Giovanni Spagnolli, Pietro Faccioli, Emiliano Biasini

{"title":"Mapping cryptic phosphorylation sites in the human proteome.","authors":"Dino Gasparotto, Annarita Zanon, Valerio Bonaldo, Elisa Marchiori, Massimo Casagranda, Erika Di Domenico, Laura Copat, Tommaso Fortunato Asquini, Marta Rigoli, Sirio Vittorio Feltrin, Nuria Lopez Lorenzo, Graziano Lolli, Maria Pennuto, Jesùs R Requena, Omar Rota Stabelli, Giovanni Minervini, Cristian Micheletti, Giovanni Spagnolli, Pietro Faccioli, Emiliano Biasini","doi":"10.1038/s44318-025-00567-1","DOIUrl":"https://doi.org/10.1038/s44318-025-00567-1","url":null,"abstract":"Advances in computational and experimental methods have revealed the existence of transient, non-native protein folding intermediates that could play roles in disparate biological processes, from regulation of protein expression to disease-relevant misfolding mechanisms. Here, we tested the possibility that specific post-translational modifications may involve residues exposed during the folding process by assessing the solvent accessibility of 87,138 post-translationally modified amino acids in the human proteome. Unexpectedly, we found that one-third of phosphorylated proteins present at least one phosphosite completely buried within the protein's inner core. Computational and experimental analyses suggest that these cryptic phosphosites may become exposed during the folding process, where their modification could destabilize native structures and trigger protein degradation. Phylogenetic investigation also reveals that cryptic phosphosites are more conserved than surface-exposed phosphorylated residues. Finally, cross-referencing with cancer mutation databases suggests that phosphomimetic mutations in cryptic phosphosites can increase tumor fitness by inactivating specific onco-suppressors. These findings define a novel role for co-translational phosphorylation in shaping protein folding and expression, laying the groundwork for exploring the implications of cryptic phosphorylation in health and disease.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The origin of septin ring size control in budding yeast. 芽殖酵母中septin环大小控制的起源。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-02 DOI: 10.1038/s44318-025-00571-5

Igor V Kukhtevich, Sebastian Persson, Francesco Padovani, Robert Schneider, Marija Cvijovic, Kurt M Schmoller

{"title":"The origin of septin ring size control in budding yeast.","authors":"Igor V Kukhtevich, Sebastian Persson, Francesco Padovani, Robert Schneider, Marija Cvijovic, Kurt M Schmoller","doi":"10.1038/s44318-025-00571-5","DOIUrl":"https://doi.org/10.1038/s44318-025-00571-5","url":null,"abstract":"The size of organelles and cellular structures needs to be tightly regulated and coordinated with overall cell size. A well-studied example is the Cdc42-driven polarization and subsequent septin ring formation in Saccharomyces cerevisiae, where the size of the resulting structures scales with cell size. However, the mechanisms underlying this scaling remain unclear. Here, we combine live-cell imaging, genetic perturbations, and three-dimensional mathematical modeling to investigate how septin ring size is controlled. Our integrative approach reveals that positive feedback in the polarization pathway, together with an increase of the amount of polarity proteins as cell size grows, can explain the scaling of the Cdc42 cluster and, consequently, septin ring diameter. Additionally, we show that in cells lacking the formin Bni1, where F-actin-cable assembly and directed polarization are disrupted, exocytosis becomes diffuse, leading to abnormally large septin rings. By integrating new experimental findings and mathematical modeling of yeast polarization, our study provides insights into the origin of septin ring size control.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RABGAP1 is a sensor that facilitates the sorting and processing of amyloid precursor protein. RABGAP1是一种促进淀粉样蛋白前体蛋白分选和加工的传感器。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1038/s44318-025-00530-0

Jessica Eden, Jonathan G G Kaufman, Conceição Pereira, Eleanor Fox, Jerome Cattin-Ortolá, Lorena Benedetti, Bart Nieuwenhuis, David J Owen, Jennifer Lippincott-Schwartz, Sean Munro, David C Gershlick

{"title":"RABGAP1 is a sensor that facilitates the sorting and processing of amyloid precursor protein.","authors":"Jessica Eden, Jonathan G G Kaufman, Conceição Pereira, Eleanor Fox, Jerome Cattin-Ortolá, Lorena Benedetti, Bart Nieuwenhuis, David J Owen, Jennifer Lippincott-Schwartz, Sean Munro, David C Gershlick","doi":"10.1038/s44318-025-00530-0","DOIUrl":"10.1038/s44318-025-00530-0","url":null,"abstract":"A hallmark of Alzheimer's disease (AD) is the accumulation of extracellular amyloid-β plaques in the brain. Amyloid-β is a 40-42 amino acid peptide generated by proteolytic processing of amyloid precursor protein (APP) via membrane-bound proteases. APP is a transmembrane protein, and its trafficking to sites of proteolysis represents a rate-limiting step in AD progression. Although APP processing has been well-studied, its trafficking itinerary and machinery remain incompletely understood. To address this, we performed an unbiased interaction screen for interactors of the APP cytosolic tail. We identified previously characterised APP binders as well as novel interactors, including RABGAP1. We demonstrated that RABGAP1 partially co-localises with APP and directly interacts with a YENPTY motif in the APP cytosolic tail. Depletion or overexpression of RABGAP1 caused mistrafficking and misprocessing of endogenous APP in human and rodent neurons. This effect is dependent on the GAP activity of RABGAP1, demonstrating that RABGAP1 affects the trafficking of APP by modulating RAB activity on endosomal subdomains. This novel trafficking mechanism has implications for other NPXY cargoes and presents a possible therapeutic avenue to explore.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"5443-5462"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIM-3 and γδ T cells: new players in breast cancer dissemination. TIM-3和γδ T细胞：乳腺癌传播的新参与者

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1038/s44318-025-00550-w

Lorenzo Galluzzi, Claudia Galassi, David L Wiest

引用次数: 0

Hemocytes facilitate interclonal cooperation-induced tumor malignancy by hijacking the innate immune system in Drosophila. 血细胞通过劫持果蝇的先天免疫系统促进克隆间合作诱导的肿瘤恶性。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-01 Epub Date: 2025-08-22 DOI: 10.1038/s44318-025-00547-5

Sihua Zhao, Yifan Guo, Xiaoyu Kuang, Xiaoqin Li, Chenxi Wu, Peng Lin, Qi Xie, Zongzhao Zhai, Du Kong, Xianjue Ma

{"title":"Hemocytes facilitate interclonal cooperation-induced tumor malignancy by hijacking the innate immune system in Drosophila.","authors":"Sihua Zhao, Yifan Guo, Xiaoyu Kuang, Xiaoqin Li, Chenxi Wu, Peng Lin, Qi Xie, Zongzhao Zhai, Du Kong, Xianjue Ma","doi":"10.1038/s44318-025-00547-5","DOIUrl":"10.1038/s44318-025-00547-5","url":null,"abstract":"Tumor heterogeneity, a hallmark of cancer, frequently leads to treatment failure and relapse. However, the intricate communication between various cell types within the tumor microenvironment and their roles in tumor progression in vivo remain poorly understood. Here we establish a novel tumor heterogeneity model in the Drosophila larval eye disc epithelium and dissect the in vivo mechanisms by combining sophisticated genetics with single-cell RNA sequencing. We found that mutation of the tricellular junction protein M6 in cells surrounding RasV12 benign tumors promotes their malignant transformation. Mechanistically, early RasV12//M6-/- tumors secrete Pvf1, which activates the Pvr receptor on hemocytes, facilitating their recruitment to the tumor site. These tumor-associated hemocytes secrete the Spätzle (Spz) ligand to activate the Toll receptor within the RasV12 tumors. This enhanced activation of the Toll pathway synergizes with RasV12 to promote malignant transformation through the JNK-Hippo signaling cascade. In summary, our study elucidates the complex interplay between genetically distinct oncogenic cells and between tumors and hemocytes, highlighting how hemocytes exploit the ancient innate immune system to coordinate tumor heterogeneity and drive tumor progression.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"5394-5428"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donor transcription suppresses D-loops in cis and promotes genome stability. 供体转录抑制顺式d环，促进基因组稳定性。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1038/s44318-025-00541-x

Yasmina Djeghmoum, Aurèle Piazza

{"title":"Donor transcription suppresses D-loops in cis and promotes genome stability.","authors":"Yasmina Djeghmoum, Aurèle Piazza","doi":"10.1038/s44318-025-00541-x","DOIUrl":"10.1038/s44318-025-00541-x","url":null,"abstract":"DNA is a substrate for competing protein-mediated activities. Whether and how transcription and the synaptic steps of recombination collide or are coordinated has not been investigated. Here, using a controlled break induction system and physical detection of D-loop DNA joint molecules in S. cerevisiae, we show that donor transcription by RNA polymerase II strongly and acutely suppresses D-loops in cis. The extent of this suppression depends on the orientation of transcription, suggesting the preferential usage of one end for the repair of DNA break in transcribed regions. Transcription-mediated D-loop suppression does not rely on endogenous transcription factors, the RNA product, or RNA:DNA hybrids. It is independent of, and can be more potent than the conserved trans D-loop-disruption factors Sgs1-Top3-Rmi1BLM-TOPO3α-RMI1/2, Mph1FANCM, and Srs2. This transcription-mediated control promotes genome maintenance by inhibiting ectopic recombination and multi-invasion-induced rearrangements, while authorizing allelic inter-homolog repair. These findings reveal the prioritization between two universal DNA-dependent processes and its role in promoting genome stability.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"5595-5617"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977194","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

Fusobacterium nucleatum interacts with cancer-associated fibroblasts to promote colorectal cancer. 核梭杆菌与癌症相关成纤维细胞相互作用促进结直肠癌。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-10-01 Epub Date: 2025-08-22 DOI: 10.1038/s44318-025-00542-w

Jessica Karta, Marianne Meyers, Fabien Rodriguez, Eric Koncina, Cedric Gilson, Eliane Klein, Monica Gabola, Mohaned Benzarti, Pau Pérez Escriva, Jose Alberto Molina Tijeras, Catarina Correia Tavares Bernardino, Falk Ponath, Anais Carpentier, Mònica Aguilera Pujabet, Maryse Schmoetten, Mina Tsenkova, Perla Saoud, Anthoula Gaigneaux, Dominik Ternes, Lidia Alonso, Nikolaus Zügel, Eric Willemssen, Philippe Koppes, Daniel Léonard, Luis Perez Casanova, Serge Haan, Michel Mittelbronn, Johannes Meiser, Vitaly I Pozdeev, Jörg Vogel, Paolo G Nuciforo, Paul Wilmes, Elisabeth Letellier

{"title":"Fusobacterium nucleatum interacts with cancer-associated fibroblasts to promote colorectal cancer.","authors":"Jessica Karta, Marianne Meyers, Fabien Rodriguez, Eric Koncina, Cedric Gilson, Eliane Klein, Monica Gabola, Mohaned Benzarti, Pau Pérez Escriva, Jose Alberto Molina Tijeras, Catarina Correia Tavares Bernardino, Falk Ponath, Anais Carpentier, Mònica Aguilera Pujabet, Maryse Schmoetten, Mina Tsenkova, Perla Saoud, Anthoula Gaigneaux, Dominik Ternes, Lidia Alonso, Nikolaus Zügel, Eric Willemssen, Philippe Koppes, Daniel Léonard, Luis Perez Casanova, Serge Haan, Michel Mittelbronn, Johannes Meiser, Vitaly I Pozdeev, Jörg Vogel, Paolo G Nuciforo, Paul Wilmes, Elisabeth Letellier","doi":"10.1038/s44318-025-00542-w","DOIUrl":"10.1038/s44318-025-00542-w","url":null,"abstract":"Gut microbial species contribute to colorectal cancer (CRC) by interacting with tumor or immune cells, however if CRC-associated bacteria engage with stromal components of the tumor microenvironment remains unclear. Here, we report interaction between the CRC-associated bacterium Fusobacterium nucleatum and cancer-associated fibroblasts (CAFs), and show that F. nucleatum is present in the stromal compartment in murine CRC models in vivo and can attach to and invade CAFs. F. nucleatum-exposed CAFs exhibit a pronounced inflammatory-CAF (iCAF) phenotype, marked by elevated expression of established iCAF markers, secretion of pro-inflammatory cytokines such as CXCL1, IL-6 and IL-8, generation of reactive oxygen species (ROS), and an increased metabolic activity. In co-culture experiments, the interaction of cancer cells with F. nucleatum-stimulated CAFs enhances invasion, a finding further validated in vivo. Altogether, our results point to a role for the tumor microbiome in CRC progression by remodeling the tumor microenvironment through its influence on cancer-associated fibroblasts, suggesting novel therapeutic strategies for targeting CRC.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"5375-5393"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0