Cell reports最新文献_第7页

Mechanical compression activates cAMP signaling in Pseudomonas aeruginosa. 机械压缩激活铜绿假单胞菌的cAMP信号。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118114

Lei Ni, Yajia Huang, Yaoxin Huang, Yue Yu, Jiarui Xiong, Hui Wen, Wenwen Xiao, Bing Li, Shuqiang Huang, Haiyi Liang, Fan Jin

{"title":"Mechanical compression activates cAMP signaling in Pseudomonas aeruginosa.","authors":"Lei Ni, Yajia Huang, Yaoxin Huang, Yue Yu, Jiarui Xiong, Hui Wen, Wenwen Xiao, Bing Li, Shuqiang Huang, Haiyi Liang, Fan Jin","doi":"10.1016/j.celrep.2026.118114","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118114","url":null,"abstract":"In Pseudomonas aeruginosa, cyclic AMP (cAMP) is a central regulator of virulence, including the type III secretion system (T3SS), yet the signals that activate cAMP remain incompletely understood. Using the real-time cAMP biosensor Gflamp1, we show that mechanical compression elevates cAMP, with an estimated activation force of approximately 3-30 nN. This mechanoresponse requires the Pil-Chp system, the FimV-FimL module, and the adenylate cyclase CyaB. Productive surface piliation and pilus extension or retraction are dispensable, whereas the major pilin PilA remains required. We further show that the histidine kinase ChpA interacts with the polar scaffold FimV and that FimL modulates FimV-dependent ChpA polar localization. Fluorescence lifetime imaging microscopy-Förster resonance energy transfer (FLIM-FRET) analysis supports compression-dependent changes in the apparent proximity of ChpA to PilG and FimL. Finally, compressed-state growth increases T3SS-associated transcription, suggesting that compression-induced cAMP signaling may link confined growth to virulence-associated gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118114"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134967","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

A near-complete quail genome identifies heterochromatin expansion and chromosome architecture remodeling. 近乎完整的鹌鹑基因组鉴定了异染色质扩展和染色体结构重塑。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118099

Jiao Liu, Qixin Guo, Shiyu Fan, Jiahong Wu, Tongyang Wang, Haoran Luo, Na Kang, Xing Li, Zhong Zhuang, Tatsuo Fukagawa, Hao Bai, Luohao Xu, Guobin Chang

{"title":"A near-complete quail genome identifies heterochromatin expansion and chromosome architecture remodeling.","authors":"Jiao Liu, Qixin Guo, Shiyu Fan, Jiahong Wu, Tongyang Wang, Haoran Luo, Na Kang, Xing Li, Zhong Zhuang, Tatsuo Fukagawa, Hao Bai, Luohao Xu, Guobin Chang","doi":"10.1016/j.celrep.2026.118099","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118099","url":null,"abstract":"Avian genomes are typically compact, with limited repetitive content, but the Japanese quail (Coturnix japonica) represents an exception. Here, we report a near-complete chromosome-level quail genome assembly (1.33 Gb), up to 43% larger than previous quail assemblies. The assembly reveals extensive repeat accumulation and heterochromatin expansion, particularly in the pericentromeric regions of micro- and dot chromosomes, and identifies a conserved centromeric repeat shared across chromosomes. Comparative analyses show that transposable element accumulation reshaped chromatin architecture, histone modification landscapes, and interchromosomal interactions. The female-specific W chromosome underwent extensive heterochromatinization and gene degeneration. Integrated epigenomic profiling further identifies quail-specific chromatin states. These findings reveal quail-specific heterochromatin expansion and provide new insights into avian centromere evolution, heterochromatin biology, and sex chromosome remodeling.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118099"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104695","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

CAR-engineered microglia harness phagocytosis to target brain tumor in organoid models. car工程小胶质细胞利用吞噬作用靶向类器官模型中的脑肿瘤。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118091

Mu Seog Choe, Woo Sub Yang, Bilal Cakir, Ferdi Ridvan Kiral, Jonghun Kim, Cynthia Lo, Eena Cheng, Benjamin Ongnok, Viswanathan Muthusamy, Nipon Chattipakorn, Siriporn C Chattipakorn, In-Hyun Park

{"title":"CAR-engineered microglia harness phagocytosis to target brain tumor in organoid models.","authors":"Mu Seog Choe, Woo Sub Yang, Bilal Cakir, Ferdi Ridvan Kiral, Jonghun Kim, Cynthia Lo, Eena Cheng, Benjamin Ongnok, Viswanathan Muthusamy, Nipon Chattipakorn, Siriporn C Chattipakorn, In-Hyun Park","doi":"10.1016/j.celrep.2026.118091","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118091","url":null,"abstract":"Glioblastoma (GBM) is among the most aggressive and lethal brain tumors, and standard treatment offers only modest survival benefits. Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematologic cancers, but its efficacy in GBM remains limited. Here we develop a CAR-engineered microglia (CAR-MG) platform and an organoid-based framework to test whether programmable microglial phagocytosis can be directed against GBM. We isolate microglia (MG) from human cortical organoids and engineer them to express a CAR targeting EGFRvIII, a recurrent tumor-specific EGFR deletion variant in GBM. In a 2D co-culture, CAR-MG selectively eliminates GBM cells through phagocytosis. In a 3D GBM-cortical organoid model, CAR-MG infiltrates tumor sites and depletes GBM cells over extended culture. Single-cell RNA sequencing (scRNA-seq) shows elevated phagocytic pathways in CAR-MG and detects internalized tumor-derived transcripts, which resolve phagocytosis-resistance programs. These results support CAR-MG as a myeloid CAR modality for human brain organoid models.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118091"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126669","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

P4-ATPase BbCrpa2 detoxifies cyclosporine a via AP2-clathrin-dependent endocytic pathway in Beauveria bassiana. p4 - atp酶BbCrpa2通过ap2 -网格蛋白依赖的内吞途径解毒环孢素a。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118064

Hui Ren, Yujie Li, Lian Ma, Jianjun Chen, Xianbi Li, Fanlong Wang, Renyu Dai, Dan Jin, Yanhua Fan, Yan Pei

{"title":"P4-ATPase BbCrpa2 detoxifies cyclosporine a via AP2-clathrin-dependent endocytic pathway in Beauveria bassiana.","authors":"Hui Ren, Yujie Li, Lian Ma, Jianjun Chen, Xianbi Li, Fanlong Wang, Renyu Dai, Dan Jin, Yanhua Fan, Yan Pei","doi":"10.1016/j.celrep.2026.118064","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118064","url":null,"abstract":"Cyclosporine A (CsA) exerts potent intracellular toxicity in fungi, yet the mechanisms underlying fungal CsA tolerance remain poorly understood. Here, we identify BbCrpa2, a P4-ATPase in the entomopathogenic fungus Beauveria bassiana, as a key determinant of CsA resistance. Unlike the trans-Golgi network-localized BbCrpa, which sequesters cytosolic CsA, BbCrpa2 functions as a plasma membrane gatekeeper. It captures CsA at the cell surface and mediates its internalization into vesicles through AP2-clathrin-dependent endocytosis. Genetic and functional analyses reveal that BbCrpa2 and BbCrpa act independently and additively to protect against CsA toxicity. BbCrpa2 constitutes the primary defense by limiting the free entry of CsA into the cytoplasm, whereas BbCrpa serves as a secondary safeguard by sequestering the residual cytosolic CsA. Together, these findings demonstrate that spatially distinct P4-ATPases cooperate to coordinate vesicular CsA transport, revealing a previously unrecognized, multi-tiered defense mechanism that enables fungal tolerance to toxic secondary metabolites.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118064"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126829","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

A single residue in the Gc protein dictates neutralization sensitivity and virulence in SFTSV. Gc蛋白中的单个残基决定了中和对SFTSV的敏感性和毒力。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118098

Xiaoyu Zhang, Xuekai Zhang, Peipei Yang, Yuxuan Li, Mingqing Lu, Juhong Rao, Rong Qu, Xue Hu, Chao Shan

{"title":"A single residue in the Gc protein dictates neutralization sensitivity and virulence in SFTSV.","authors":"Xiaoyu Zhang, Xuekai Zhang, Peipei Yang, Yuxuan Li, Mingqing Lu, Juhong Rao, Rong Qu, Xue Hu, Chao Shan","doi":"10.1016/j.celrep.2026.118098","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118098","url":null,"abstract":"Severe fever with thrombocytopenia syndrome virus (SFTSV), a World Health Organization (WHO) priority pathogen, causes hemorrhagic fever with up to 30% case fatality and lacks approved vaccines or therapeutics. Here, we isolated Gc-specific monoclonal antibodies H2, H4, and H12. H2 potently neutralized endemic Chinese SFTSV strains but failed against the heterologous NB24 strain. Mutational analysis identified Arg577 within Gc domain I as a critical residue essential for H2 binding. Reverse genetics demonstrated that Arg577 is both necessary for H2 binding and sufficient to confer neutralization susceptibility. Beyond immune recognition, residue 577 critically governed viral replication fitness and pathogenesis. In virulent HBMC, Arg577 was essential for efficient replication, assembly and overall viral fitness; in attenuated NB24 (native lysine), introducing Arg577 enhanced progeny production and virulence. Combining H2 with H12 overcame H2's narrow neutralization, achieving broad protection. Our study establishes Arg577 as a central regulator of SFTSV pathogenicity and informs dual-antibody therapy development.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118098"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126676","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

Explainable AI-driven marker selection and development of EastFocus AISNPplex 61 assay for fine-scale biogeographical ancestry inference. 可解释的人工智能驱动的标记选择和EastFocus AISNPplex 61检测的开发，用于精细尺度的生物地理祖先推断。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118011

Meiming Cai, Lisiteng Luo, Yue Liu, Xi Wang, Xiaolian Wu, Qinglin Liang, Chanjun Zhuo, Yuyang Li, Chao Liu, Zhe Zhou, Bofeng Zhu

{"title":"Explainable AI-driven marker selection and development of EastFocus AISNPplex 61 assay for fine-scale biogeographical ancestry inference.","authors":"Meiming Cai, Lisiteng Luo, Yue Liu, Xi Wang, Xiaolian Wu, Qinglin Liang, Chanjun Zhuo, Yuyang Li, Chao Liu, Zhe Zhou, Bofeng Zhu","doi":"10.1016/j.celrep.2026.118011","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118011","url":null,"abstract":"A hierarchical ancestry inference framework was developed to resolve continental and fine-scale East Asian population structures for forensic applications. Combining the shapley additive explanations (SHAP) method with recursive feature elimination, 58 ancestry informative single-nucleotide polymorphisms (AIM-SNPs) were selected. A self-developed 6-dye allele-specific PCR multiplex system (EastFocus AISNPplex 61) was established, integrating these AIM-SNPs, two Y-chromosomal InDels, and the Amelogenin locus. Validation demonstrated reliable single-source genotyping down to 250-500 pg and full minor contributor recovery in mixed DNA samples up to a 1:7 ratio (125 pg minor input). Population genetic and automated machine learning analyses confirmed that the panel distinguished five continental populations (with category-specific area under the curve (AUC) values ranging from 0.981 to 0.999) and differentiated intra-East Asian structures (with all cluster-specific AUC values exceeding 0.940). Integrating model probabilities with dimensionality reduction enabled two-dimensional spatial mapping to visualize genetic affinities and admixture patterns in studied populations. This workflow provides a practical, interpretable, and capillary electrophoresis-compatible solution for forensic biogeographical ancestry inference and micro-genetic structure mapping.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118011"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104794","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

Genome-wide CRISPR screening identified hemojuvelin as a non-neuronal receptor for the botulinum neurotoxin serotypes A and C. 全基因组CRISPR筛选鉴定了haemjuvelin是肉毒杆菌神经毒素血清型a和C的非神经元受体。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118106

Wantong Ma, Bo Liu, Jingjing Gao, Rong Nie, Ziye Liu, Wenrui Wang, Yu Wang, Guihua Ning, Chengmu Zhao, Yudong Wang, Xinrui Yue, Dang Ding, Xinyao Ma, Jinghan He, Xiaoru Wang, Fuwei Qi, Yali Liu, Fudi Wang, Xin Wang, Dejuan Zhi, Dongsheng Wang

{"title":"Genome-wide CRISPR screening identified hemojuvelin as a non-neuronal receptor for the botulinum neurotoxin serotypes A and C.","authors":"Wantong Ma, Bo Liu, Jingjing Gao, Rong Nie, Ziye Liu, Wenrui Wang, Yu Wang, Guihua Ning, Chengmu Zhao, Yudong Wang, Xinrui Yue, Dang Ding, Xinyao Ma, Jinghan He, Xiaoru Wang, Fuwei Qi, Yali Liu, Fudi Wang, Xin Wang, Dejuan Zhi, Dongsheng Wang","doi":"10.1016/j.celrep.2026.118106","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118106","url":null,"abstract":"Botulinum neurotoxins (BoNTs) enter cells primarily through neuronal receptors and gangliosides. However, the mechanism that enables their specific accumulation at neuromuscular junctions (NMJs) remains poorly understood. In this study, a genome-wide CRISPR-Cas9 screen identifies hemojuvelin (HJV), a membrane protein abundant in skeletal muscle, as a non-neuronal receptor for BoNT/A and BoNT/C. Knockout and rescue experiments show that HJV mediates toxin binding by a direct interaction between its C-terminal region (residues 155-393) and the toxin WY loop within the receptor-binding domain (HCR). In mice, HJV knockout markedly reduces toxin enrichment on the sarcolemma and significantly attenuates toxin sensitivity such as digital paralysis and lethality. Thus, HJV captures these toxins on the muscle sarcolemma, establishing a critical prerequisite for efficient recognition and internalization by neuronal receptors at NMJs. These findings further refine the entry mechanism of BoNTs in vivo and offer actionable insights for treating BoNT intoxication and for optimizing their clinical applications.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118106"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104763","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

Bacterial endosymbiont suppresses detoxification through folate-mediated DNA methylation in Nilaparvata lugens. 细菌内共生体通过叶酸介导的DNA甲基化抑制褐藻的解毒作用。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118103

Yuanyuan Gao, Tingwei Cai, Xiaoqian Wang, Pol Nadal-Jimenez, Chengyue Li, Chunyan Su, Shun He, Jianhong Li, Hu Wan

{"title":"Bacterial endosymbiont suppresses detoxification through folate-mediated DNA methylation in Nilaparvata lugens.","authors":"Yuanyuan Gao, Tingwei Cai, Xiaoqian Wang, Pol Nadal-Jimenez, Chengyue Li, Chunyan Su, Shun He, Jianhong Li, Hu Wan","doi":"10.1016/j.celrep.2026.118103","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118103","url":null,"abstract":"Symbiont-derived metabolites can regulate host physiology, but how they affect xenobiotic detoxification remains poorly understood. Here, we provide evidence that the endosymbiont Arsenophonus nilaparvatae increases insecticide susceptibility in Nilaparvata lugens through a folate-associated DNA methylation pathway. Specifically, A. nilaparvatae enhances folate biosynthesis through metabolic complementation with host alkaline phosphatase, while folate supplementation reduces P450 expression and monooxygenase activity. Metabolomics reveals an increased ratio of S-adenosylmethionine to S-adenosylhomocysteine (SAM/SAH). Consistent with this shift, symbiont infection and folate treatment are accompanied by increased NlDNMT3 expression and global 5-methylcytosine (5mC) levels. Moreover, genome-wide and targeted bisulfite analyses identify increased promoter-associated methylation at NlCYP6ER1, coinciding with reduced transcription. Importantly, inhibiting DNA methylation partially reverses these molecular and phenotypic effects. Finally, folate-associated sensitization is observed with high-folate transgenic rice and in other tested insects. Together, these findings support a symbiont-folate-DNA methylation axis regulating host detoxification and suggest folate metabolism as a potential target for insect control.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118103"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104711","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

Deoxysphingolipids activate cGAS-STING and enhance antitumor immunity. 脱氧鞘脂激活cGAS-STING，增强抗肿瘤免疫。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118089

Suchandrima Saha, Fabiola N Velazquez, Fatemeh Dehpanah, Brianna L Bergfalk, Samantha Mulkeen, Karissa J Lopez, Cungui Mao, David C Montrose

{"title":"Deoxysphingolipids activate cGAS-STING and enhance antitumor immunity.","authors":"Suchandrima Saha, Fabiola N Velazquez, Fatemeh Dehpanah, Brianna L Bergfalk, Samantha Mulkeen, Karissa J Lopez, Cungui Mao, David C Montrose","doi":"10.1016/j.celrep.2026.118089","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118089","url":null,"abstract":"Deoxysphingolipids (deoxySLs) are a class of non-canonical sphingolipids that can adversely impact mitochondrial function. Mitochondrial DNA release resulting from mitochondrial disruption can activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, and in turn, promote antitumor immunity. Here, we investigated whether inducing deoxySL accumulation in colon cancer cells drives immune-specific, antitumor effects. We show that depleting serine increased deoxySLs and enhanced immune cell infiltration in colon tumors, in parallel with suppressing tumor growth. Elevating tumor deoxySL levels in mice through mutation of serine palmitoyltransferase and feeding a high alanine diet exerted similar effects, including immune-mediated tumor growth suppression. Work conducted in multiple in vitro systems identified deoxySLs as key triggers of cGAS-STING activation, an effect mediated by the release of mitochondrial DNA under mitochondrial stress. Collectively, these findings demonstrate that deoxySLs drive antitumor immunity and identify a previously unrecognized metabolic strategy for cancer therapy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118089"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126658","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

Molecular stratification of SPOP-mutant prostate cancer demonstrates Wnt signaling and replication stress signatures in diverse patient populations. spop突变前列腺癌的分子分层在不同患者群体中显示了Wnt信号和复制应激特征。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-06 DOI: 10.1016/j.celrep.2026.118006

Kinza Rizwan, Sai Prasada Rao Manikonda, Heidi Dowst, Patricia Castro, Maria Elisa Ruiz Echartea, Cristian Coarfa, Michael Ittmann, Neda Zarrin-Khameh, Quillan Huang, Martha Mims, Salma Kaochar

{"title":"Molecular stratification of SPOP-mutant prostate cancer demonstrates Wnt signaling and replication stress signatures in diverse patient populations.","authors":"Kinza Rizwan, Sai Prasada Rao Manikonda, Heidi Dowst, Patricia Castro, Maria Elisa Ruiz Echartea, Cristian Coarfa, Michael Ittmann, Neda Zarrin-Khameh, Quillan Huang, Martha Mims, Salma Kaochar","doi":"10.1016/j.celrep.2026.118006","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118006","url":null,"abstract":"Speckle-type POZ protein (SPOP) mutations define a molecular subtype of prostate cancer, but their genomic and transcriptional features across racially diverse populations remain incompletely resolved. We integrated tumor genomic profiles from 273 patients, including 40 SPOP-mutant tumors, with RNA sequencing from 102 cases to characterize SPOP-associated alterations across disease stage and self-reported race. SPOP-mutant tumors showed significant enrichment of APC and other recurrent co-alterations, supporting Wnt pathway dysregulation as a defining genomic feature. Transcriptomic analysis revealed enhanced proliferative, metabolic, and biosynthetic programs accompanied by suppression of extracellular matrix, structural, and differentiation-associated pathways. Race-stratified analyses identified a conserved repression of structural programs but divergent transcriptional activation states: African American SPOP-mutant tumors preferentially exhibited inflammatory, hypoxic, and epithelial plasticity programs, whereas Caucasian tumors showed stronger MYC, oxidative phosphorylation, translational, and androgen-response signatures. These findings define SPOP-mutant prostate cancer as a molecularly distinct, context-dependent disease subtype with potentially heterogeneous, clinically relevant therapeutic vulnerabilities across patient populations.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118006"},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126802","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