Journal of Cell Communication and Signaling最新文献

{"title":"Rapid normal fibroblast-tumor crosstalk promotes cancer-associated fibroblast-like activation and attenuates mitomycin C cytotoxicity in bladder cancer","authors":"Jinhui Gao,&nbsp;Cindy Xinyu Ji,&nbsp;Ci Ren,&nbsp;John Hines,&nbsp;Eleanor Stride,&nbsp;Richard T. Bryan,&nbsp;Jennifer L. Rohn","doi":"10.1002/ccs3.70110","DOIUrl":"10.1002/ccs3.70110","url":null,"abstract":"<p>Normal fibroblasts (NFs) are among the earliest stromal cells encountered by bladder cancer cells during invasion into the lamina propria, yet their contribution to tumor progression and intravesical chemotherapy response remains poorly defined. Here, we investigated whether NFs are passive stromal bystanders or active participants in early bladder cancer microenvironmental remodeling. Analysis of an early-stage non-muscle-invasive bladder cancer transcriptomic cohort revealed that fibroblast-associated scores were higher in T1 than Ta tumors, enriched in European Organisation for Research and Treatment of Cancer high-risk disease, positively correlated with epithelial-mesenchymal transition (EMT) scores, and associated with increased expression of resistance-linked genes. Experimentally, fibroblast-conditioned medium reduced bladder cancer cell proliferation while accelerating wound closure, indicating a less proliferative but more motile phenotype. This was accompanied by EMT-like cadherin remodeling, including reduced E-cadherin and increased N-cadherin staining. Reciprocally, tumor-derived signals rapidly induced cancer-associated fibroblast (CAF)-like activation features in NFs within 48 h, including increased α-smooth muscle actin, fibroblast activation protein, and PDGFRβ expression. Functionally, increasing fibroblast-to-tumor cell ratios progressively attenuated mitomycin C (MMC)-induced cytotoxicity, demonstrating that stromal context can modify chemotherapy response in vitro. Together, these findings show that NF-tumor crosstalk is rapid, bidirectional and functionally relevant to MMC response in vitro. Rather than acting only after stable CAF formation, NFs can rapidly acquire CAF-like activation features following tumor-derived stimulation and contribute to a stromal context associated with EMT-like plasticity and reduced MMC-induced cytotoxicity in vitro.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of TKS4 isoforms and their role in cellular processes in breast cancer","authors":"Serhii Kropyvko,&nbsp;Nazar Shevchuk,&nbsp;Olga Gubar,&nbsp;Kyrylo Lavrynenko,&nbsp;Yaroslav Nemesh,&nbsp;Denys Kozakov,&nbsp;Valentyn Polishchuk,&nbsp;Valentyna Kryklyva,&nbsp;Liubov Syvak,&nbsp;Nataliia Verovkina,&nbsp;Tetyana Gryaznova","doi":"10.1002/ccs3.70100","DOIUrl":"https://doi.org/10.1002/ccs3.70100","url":null,"abstract":"<p>The scaffold protein TKS4 plays a role in the development of several cancers. Alternative splicing of the <i>TKS4</i> gene generates two isoforms, TKS4L and TKS4b; however, their distinct expression patterns and functional roles have not yet been characterized. We have shown that TKS4 isoforms were differentially expressed across human cell lines and breast cancer (BC) tumor samples. Both <i>TKS4L</i> and <i>TKS4L</i>/<i>TKS4b</i> mRNA ratios were significantly altered in tumors compared with adjacent tissues. We identified six novel binding SRC homology 3-domain-containing partners for TKS4L, none of which interact with TKS4b, suggesting their functional differences. Tyrosine phosphorylation of both isoforms was induced by Src(Y527F) kinase overexpression, enabling binding to the SH2 domains of signaling proteins. Interestingly, TKS4b significantly accumulated in the nucleus, whereas TKS4L was primarily present in the cytosol in MCF-7 cells. TKS4b overexpression enhanced MCF-7 cell migration. Both TKS4 isoforms exhibit oncogenic properties by promoting epithelial–mesenchymal transition in BC cells, highlighting their potential as targets for therapeutic intervention.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Homeobox B13 activates the hypoxia-inducible factor 1 pathway through histone lactylation thereby reprogramming lipid metabolism and promoting sorafenib resistance in hepatocellular carcinoma”","authors":"","doi":"10.1002/ccs3.70095","DOIUrl":"https://doi.org/10.1002/ccs3.70095","url":null,"abstract":"<p>Xie, Qingqing, Fangxia Teng, Ting Ding, Huaizhe Zhang, Jian Huang, and Shu Zhang. 2026. “Homeobox B13 activates the hypoxia-inducible factor 1 pathway through histone lactylation thereby reprogramming lipid metabolism and promoting sorafenib resistance in hepatocellular carcinoma,” <i>Journal of Cell Communication and Signaling</i>: e70077. https://doi.org/10.1002/ccs3.70077.</p><p>In the originally published article, in Figure 5F, the HOXB13 western blot band representing Huh7/SR cells was inadvertently used to display the results for HCCLM3/SR cells. This error does not affect any scientific conclusions of the article.</p><p>Additionally, in Figure 6C–G, the negative control for the knockdown experiment was incorrectly labeled as “Vector.” The correct label should be “sh NC.” This does not affect the conclusions of the article.</p><p>We apologize for this error.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevotella loescheii attenuates pregnancy-induced hypertension by reshaping placental immunity and halting macrophage pyroptosis","authors":"Jingjing Wu,&nbsp;Linlin Hu,&nbsp;Peipei Chen,&nbsp;Lihong Cai","doi":"10.1002/ccs3.70099","DOIUrl":"https://doi.org/10.1002/ccs3.70099","url":null,"abstract":"<p>Pregnancy-induced hypertension (PIH) severely impairs placental function, yet its microenvironmental alterations and potential interventions remain unclear. Here, we combined single-cell RNA sequencing (scRNA-seq) with an in vivo model to investigate the protective effects of <i>Prevotella loescheii</i> (PL) in PIH. scRNA-seq revealed that PIH reshaped placental cellular composition, reducing trophoblasts and myeloid cells while increasing smooth muscle cells, and disrupted cell–cell communication. Functional analyses identified oxidative stress (OS) and macrophage-driven pyroptosis via the NLRP3 inflammasome as key pathological features. Trajectory analysis further demonstrated the depletion of Hofbauer cells, which was restored by PL. In vivo, PL significantly alleviated PIH phenotypes, including proteinuria and placental structural damage. Mechanistically, PL reduced proinflammatory cytokines, suppressed mitochondrial OS and pyroptosis, and partially restored short-chain fatty acid metabolism. Collectively, these findings indicate that PL ameliorates PIH by modulating the placental immune microenvironment and metabolic homeostasis, providing a potential therapeutic strategy.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadening horizons: Pathogenesis and therapeutics of renal ciliopathies","authors":"Qiaowei Zhang,&nbsp;Shuwen Xue,&nbsp;Zhi Gao,&nbsp;Panlai Shi,&nbsp;Li Wang,&nbsp;Qi Feng,&nbsp;Xiangdong Kong,&nbsp;Xiaofan Zhu","doi":"10.1002/ccs3.70102","DOIUrl":"10.1002/ccs3.70102","url":null,"abstract":"<p>Renal ciliopathies encompass a spectrum of genetic disorders arising from structural or functional impairments of primary cilia, specialized organelles critical for mechanosensation and signal transduction within renal epithelial cells. These disorders are characterized by cystogenesis, driven by dysregulated ciliary signaling, leading to uncontrolled epithelial proliferation, aberrant growth, and loss of cellular polarity. The clinical trajectory evolves from initial cyst formation to advanced tubulointerstitial fibrosis and progressive renal failure. This progression is governed by pathogenic variants in genes encoding ciliary proteins. While advancements in genetic testing have established prenatal diagnosis as a pivotal tool for early identification, definitive diagnosis and therapeutic intervention remain challenging. These difficulties stem from several factors: incomplete understanding of the molecular mechanisms underlying cyst formation and fibrosis; limitations in prenatal diagnostic accuracy owing to phenotypic overlap and incomplete penetrance; and the marked genetic heterogeneity and diverse clinical trajectories of renal ciliopathies. Existing studies have primarily focused on unidirectional modulation of individual pathways, whereas the systematic integration of signaling network cascades remains largely unaddressed. This review systematically elucidates the molecular mechanisms and aberrant signaling pathways in renal ciliopathies, links genetic heterogeneity to clinical phenotypes, and lays a theoretical basis for prenatal diagnosis and novel therapies.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parvalbumin interneurons in Alzheimer's disease: Physiological insights and pathophysiological mechanisms","authors":"Mengyan Wu,&nbsp;Xingdong Zeng,&nbsp;Yongle Cai,&nbsp;Haonan Chen,&nbsp;Qianying Li,&nbsp;Hao Yang","doi":"10.1002/ccs3.70105","DOIUrl":"10.1002/ccs3.70105","url":null,"abstract":"<p>Fast-spiking parvalbumin-positive (PV⁺) interneurons, a specialized class of inhibitory neurons, possess unique morphological and functional properties that govern spatiotemporal precision in local microcircuits, large-scale network synchronization, and memory-related computations. Since their initial identification in the late 19th century, technological innovations in cellular neuroscience have progressively elucidated the multifaceted roles of these neurons. In this review, we first delineate the embryonic origins and developmental trajectory of PV⁺ interneurons, emphasizing their unique properties for high-frequency firing with remarkable temporal precision. These specialized features enable PV⁺ interneurons to orchestrate network oscillations and critically modulate memory encoding, consolidation, and retrieval, despite their substantial metabolic demands. We subsequently integrate multiple lines of evidence implicating region- and subtype-specific PV⁺ interneuron impairment as a pivotal pathological hallmark in Alzheimer's disease (AD). Furthermore, we dissect molecular and cellular mechanisms driving PV⁺ interneuron dysfunction in AD, including numerical alterations, morphological remodeling, and electrophysiological disruptions. Critically, we propose that the pathological transformation of PV⁺ interneuron physiology emerges as a key driver in AD progression, bridging cellular dysfunction to system-level cognitive failure.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shikonin promotes osteogenic differentiation of periodontal ligament stem cells by modulating the p38 MAPK/ETS transcription factor 1/cementum protein 1 axis in vitro","authors":"Zeyu Wu,&nbsp;Chao Shan,&nbsp;Jie Song,&nbsp;Qian Yu,&nbsp;Bing-jie Lian,&nbsp;Jin Zhao","doi":"10.1002/ccs3.70104","DOIUrl":"10.1002/ccs3.70104","url":null,"abstract":"<p>Periodontitis is a common disorder that causes tooth loss. Osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is crucial for repairing periodontal defects. This study aimed to investigate the underlying mechanism by which Shikonin promotes the osteogenic differentiation of PDLSCs. PDLSCs were isolated from the periodontal ligaments of orthodontically extracted premolars. Flow cytometry was used to characterize the cell surface markers of PDLSCs. PDLSCs were cultured in osteogenic induction medium and treated with Shikonin. Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining were used to evaluate ALP activity and assess calcium nodule formation, respectively. Protein levels were determined by Western blot analysis. A dual-luciferase reporter assay and chromatin immunoprecipitation analysis confirmed the interaction between the ETS transcription factor 1 (ELK1) and <i>cementum protein 1 (CEMP1)</i> promoter. Shikonin promoted the osteogenic differentiation of PDLSCs (about 7.6 folds for ALP staining and about 6.9 folds for ARS staining with 1 μm Shikonin, <i>p</i> &lt; 0.01). Shikonin-mediated enhancement of osteogenic differentiation was achieved by promoting the phosphorylation of ELK1 through the activation of the p38 MAPK signaling pathway (<i>p</i> &lt; 0.05). Moreover, ELK1 accelerated osteogenic differentiation and transcriptionally activated CEMP1 expression (<i>p</i> &lt; 0.05). Activation of the ELK1/CEMP1 axis contributed to Shikonin-induced osteogenic differentiation of PDLSCs (<i>p</i> &lt; 0.05). Shikonin promotes the osteogenic differentiation of PDLSCs in vitro by modulating the p38 MAPK/ELK1/CEMP1 axis.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report on the 13th international workshop on the CCN family of genes and inaugural ARBIOCOM conference, Nice, France","authors":"Bernard Perbal,&nbsp;Ralf Weiskirchen,&nbsp;Annick Perbal,&nbsp;Brahim Chaqour","doi":"10.1002/ccs3.70096","DOIUrl":"10.1002/ccs3.70096","url":null,"abstract":"<p>The 13th International Workshop on the CCN Family of Genes, held in Nice as part of the inaugural ARBIOCOM World Conference, brought together investigators with diverse research backgrounds, disciplines, and expertise. Building on the long-standing mission of the International CCN Society and the expanding ARBIOCOM initiative, the meeting highlighted the growing importance of interdisciplinary exchange in accelerating discovery in normal and pathological signaling networks. Scientific sessions featured presentations by renowned speakers and early-career investigators alike, creating a highly collaborative environment that fostered discussion of emerging concepts and translational opportunities. Among the major themes, this joint conference-meeting highlighted “hot” research topics such as the nuclear and extracellular roles of CCN proteins in regulating gene expression, tissue development and remodeling, stem cell differentiation and therapies, and disease initiation and progression. Presentations on skeletal biology emphasized how extracellular matrix proteins and matricellular factors shape bone, cartilage, and connective tissue development and pathology, whereas vascular sessions revealed new mechanistic links between extracellular cues, endothelial remodeling, macrophage-driven vessel regression and vascular smooth muscle homeostasis. Other talks extended the relevance of new signaling molecules in intestinal regeneration, hepatic inflammation, metabolic control, and cancer progression, illustrating the broad biological reach of these pathways. The meeting also emphasized the value of integrating new model systems, advanced single-cell approaches, and functional in vivo studies to uncover mechanisms that were previously unknown. Collectively, the scientific sessions and discussions identified and filled key knowledge gaps and generated new hypotheses with strong potential for future discoveries. By connecting established expertise with complementary scientific perspectives, this meeting provided a fertile platform for cross-pollination of ideas and highlighted several avenues for future research aimed at developing novel diagnostic and therapeutic strategies and tools.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol exposure promotes cell communication network 1 cleavage in esophageal adenocarcinoma cells exclusively","authors":"Wula Aladan,&nbsp;Baoxin Chi,&nbsp;Zhiheng Chang,&nbsp;Mizhu Wang,&nbsp;Tong Dang,&nbsp;Xianmei Meng,&nbsp;Jianyuan Chai","doi":"10.1002/ccs3.70103","DOIUrl":"10.1002/ccs3.70103","url":null,"abstract":"<p>Alcohol consumption has been a risk factor for more than 200 diseases, including esophageal cancer. Cell communication network 1 (CCN1), a matricellular protein, is highly expressed in esophageal squamous cell carcinoma (ESCC) but is barely detectable in esophageal adenocarcinoma (EAC). Alcohol consumption has been identified as a major contributor to ESCC development, but its role in EAC is uncertain. This study examines the impact of acute (30 min) or prolonged (12 h) alcohol exposure (5, 100, and 500 mM) on CCN1 expression and function in esophageal epithelial cells, including normal (HEEC), ESCC (KYSE150 and KYSE410), and EAC (OE19 and OE33), in association with the activity of MMP2, MMP9, and MMP14. It was found that alcohol exposure promoted CCN1 expression in both normal and tumor cells but induced CCN1 cleavage exclusively in EAC cells, generating an 18-kDa fragment that promotes tumor growth. MMP9, which was active only in EAC cells, was found to mediate this cleavage. Forced activation of MMP9 in either normal or ESCC cells improved cell viability, whereas inhibition of MMP9 in EAC cells attenuated cell survival. Taken together, alcohol exposure promotes MMP9-mediated CCN1 cleavage in EAC, converting CCN1 from a pro-death to a pro-survival factor for EAC. This makes alcohol consumption a risk factor not only for ESCC development but also for EAC progression. A preprint can be found at d197for5662m48.cloudfront.net.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The suppressor of cytokine signaling 3 regulates glioma stem cell maintenance and immune microenvironment through signal transducer and activator of transcription 3 signaling","authors":"Jingtao Wang,&nbsp;Gaolei Hou,&nbsp;Zhaofei Song,&nbsp;Kai Gao,&nbsp;Hongbin Wang,&nbsp;Tao Li","doi":"10.1002/ccs3.70041","DOIUrl":"https://doi.org/10.1002/ccs3.70041","url":null,"abstract":"<p>This study aims to elucidate the role of suppressor of cytokine signaling 3 (SOCS3) in glioma stem cells (GSCs) via single-cell RNA sequencing (scRNA-seq), focusing on its regulation of STAT3-mediated self-renewal, apoptosis resistance, and tumor microenvironment (TME) remodeling. ScRNA-seq data from 19 high-grade glioma patients were analyzed using Seurat, Harmony, and SingleR for clustering, annotation, and SOCS3 stratification (SOCS3-High: <i>n</i> = 4; SOCS3-Low: <i>n</i> = 15). Differential gene analysis, pathway enrichment, and CellChat were employed for TME characterization. In vitro, SOCS3-overexpressing/silenced GSC11 models were tested via MTT, TUNEL, neurosphere assays, and STAT3 pathway modulation (IL-6). In vivo, intracranial xenografts in nude mice evaluated tumor growth and survival. SOCS3 was downregulated in GSCs and neurons. SOCS3-Low GSCs exhibited 777 differentially expressed genes enriched in T-cell receptor, p53, and JAK-STAT axis, suppressed T-cell/microglia infiltration, and promoted oligodendrocyte precursor cell/astrocyte survival. SOCS3 overexpression reduced GSC proliferation, induced apoptosis, inhibited neurosphere formation, and suppressed STAT3 phosphorylation and stemness markers (OCT4/SOX2/NANOG). IL-6 reactivated STAT3, reversing SOCS3-mediated tumor suppression. In vivo, SOCS3 overexpression attenuated tumor growth and prolonged survival, counteracted by IL-6. Low SOCS3 expression contributes to glioma progression by promoting STAT3 activation and an immunosuppressive TME. Targeting the SOCS3-STAT3 axis may offer therapeutic potential.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}