Cell Communication and Signaling最新文献

{"title":"Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.","authors":"Mei Wang, Yue Mi, Qinong Ye","doi":"10.1186/s12964-026-03080-y","DOIUrl":"10.1186/s12964-026-03080-y","url":null,"abstract":"<p><p>Breast cancer (BC) development is influenced by multifactorial mechanisms. Despite significant advancements in early diagnostic techniques and comprehensive therapeutic approaches, BC continues to pose a substantial threat to women's health, exhibiting persistently high incidence and mortality rates. The Notch signaling pathway, a highly conserved evolutionary pathway initially identified in Drosophila, has garnered extensive research interest and is implicated in the pathogenesis of diverse malignancies, including BC. However, accumulating evidence reveals a highly context-dependent role for Notch signaling in cancer, with documented functions ranging from oncogenic to tumor-suppressive depending on the specific cellular and microenvironmental context. Current evidence indicates that Notch1-4 display nonredundant functional divergence in BC. In this review, we discuss how receptor-specific regulatory mechanisms shape distinct Notch1-4 signaling outputs and summarize the context-dependent functions and molecular mechanisms of Notch receptors across tumor-cell states, BC molecular subtypes, and tumor microenvironmental components. We also review current advances and limitations in pan-Notch inhibition and receptor-specific targeting strategies, aiming to provide clearer directions for future Notch receptor-targeted therapy in BC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.","authors":"Jiayi Ye, Yijun Zhao, Shuyang Mao, Xingxing Li, Zitong Wang, Xin Li, Xinchen Xu, Minqi Tao, Chunhai Xiao, Qingqing Huang, Gang Huang, Wei Xie","doi":"10.1186/s12964-026-03084-8","DOIUrl":"10.1186/s12964-026-03084-8","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a dynamic and constantly evolving milieu surrounding cancer cells, comprising numerous components that influence tumor growth. The Carcinoembryonic Antigen-Related Cell Adhesion Molecule (CEACAM) family has been found to be abnormally expressed in various cancers, and recent studies have highlighted its critical role in shaping and regulating the TME. Several antibody drugs targeting the CEACAM family have been developed over the last years. However, due to the physiological expression of CEACAMs in normal tissues, most of these targeted agents have yielded unsatisfactory clinical trial outcomes, characterized by significant toxicity and limited efficacy. In view of this, enhancing therapeutic efficacy while reducing adverse effects has become a focal point of current research. This review systematically summarizes the structural features of the CEACAM family and the intrinsic mechanistic differences underlying their tumor-promoting effects, and discusses the limitations of existing clinical drugs. Based on antibody optimization strategies, we propose a conceptual framework of \"dual-recognition\" antibodies and elaborate on precision targeting approaches at three levels-epitope, molecular, and environmental-to provide directional guidance for future investigations.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis drives vascular hyperpermeability in acute lung injury via lactate-GPR81 axis in endothelial cells.","authors":"Kun Chen, Kerui Fan, Jiao Wang, Xinyan Zan, Honghong Zhou, Jing Song, Yongqiang Yang, Kai Hu, Ying Zhi, Jingyuan Wan, Hongzhong Li, Sheng Cheng, Xiaojun Ren, Min Zhu, Yu Jiang, Gang Liu, Li Zhang","doi":"10.1186/s12964-026-03070-0","DOIUrl":"10.1186/s12964-026-03070-0","url":null,"abstract":"<p><p>A growing body of evidence suggests that enhanced glycolysis profoundly reprograms inflammatory response in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS), but the underlying mechanisms largely remain unclear. Lactate is the end-product of glycolysis, which has been recently found to function as a bioactive metabolite via G-protein coupled receptor 81 (GPR81). In the present study, the potential roles of lactate-GPR81 axis were investigated in mice with lipopolysaccharide (LPS)-induced ALI. The results indicated that LPS challenge increased the level of lactate in bronchoalveolar lavage fluid (BALF). Pharmacological suppression of glycolysis or inhibition of lactate dehydrogenase decreased lactate level and alleviated lung injury, but supplementation with lactate or a GPR81 agonist exacerbated lung injury. Global deletion of GPR81 or endothelial-specific deletion of GPR81, but not myeloid-specific deletion of GPR81, resulted in alleviated lung injury. In endothelial cells, the differentially expressed genes (DEGs) in RNA-seq after lactate supplementation were enriched in cAMP signaling pathway. Consistently, supplementation with lactate resulted in decline of cAMP, reduction of VE-cadherin and enhanced phosphorylation of myosin light chain 2 (MLC2) in endothelial cells, whereas knockdown of GPR81 reversed these effects. In addition, the modulation of lactate/GPR81 on cAMP, VE-cadherin and MLC2 was validated in GPR81 knockout mice. Importantly, the elevation of lactate is positively correlated with the degree of protein leakage, the level of proinflammatory cytokines in BALF and APACHE II score from patients with ARDS. Taken together, the present study suggests that endothelial GPR81 molecularly bridges glycolysis and inflammation, which drives microvascular hyperpermeability and the development of ALI.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 IGF2-ERK-Fos axis drives a Müller cell glial-mesenchymal transition-like response to disrupt retinal homeostasis in early myopia.","authors":"Jiaojiao Feng, Xiaoqi Gong, Yibo Han, Yunxiao Xie, Anfeng Luo, Hongtao Li, Wei Zhang, Jing Li, Xiaoyun Dong, Shuhan Li, Han Yu, Jike Song, Hongsheng Bi","doi":"10.1186/s12964-026-03088-4","DOIUrl":"10.1186/s12964-026-03088-4","url":null,"abstract":"<p><p>Myopia is increasingly recognized as a complex pathology involving retinal remodeling, yet the cellular mechanisms linking early visual stress to this process remain unclear. This study investigated whether Müller glial (MG) cells undergo a glial-mesenchymal transition (GMT)-like response in early myopia and identified the upstream signaling axis driving this transformation. We integrated single-cell and spatial transcriptomic analyses to construct a high-resolution atlas of retinal cell heterogeneity in a guinea pig model of form-deprivation myopia (FDM). Single-cell analysis revealed an expanded MG population (18.9% vs. 6.9%) and identified a disease-enriched Fos⁺ MG subcluster exhibiting a transcriptional signature of GMT and activated extracellular matrix (ECM) remodeling. IGF2 signaling was elevated in myopic MG cells and correlated with ERK/Fos activation. In vivo siIGF2 attenuated myopia progression, preserved retinal function/structure, suppressed MG activation/proliferation and GMT/ECM marker expression, and reduced inner limiting membrane abnormalities and retinal stiffening. Conversely, in vitro, rhIGF2 activated the ERK/Fos pathway, promoting proliferation, migration, GMT-like response, and collagen synthesis in MIO-M1 cells. These findings demonstrate that early myopia involves Fos⁺ MG-driven retinal remodeling via GMT-like response, coupling visual stress to ECM and mechanical changes. The IGF2-ERK-Fos axis is a key upstream driver of this pathology, presenting a novel target for intervention to preserve retinal homeostasis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet homeostasis and heterogeneity in inflammation and sepsis: mechanisms, biological effects, and clinical potential.","authors":"Yiyun Pan, Wenling Zhao, Beibei Yu, Ji Zhang, Mengdi Qu, Ruiwen Jiang, Tingye Xu, Dongliang Li, Hao Zhang, Changhong Miao","doi":"10.1186/s12964-026-03061-1","DOIUrl":"10.1186/s12964-026-03061-1","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome resulting from a dysregulated host immune response to infection and is frequently accompanied by coagulation abnormalities and multiple organ dysfunction. As central regulators at the intersection of hemostasis, inflammation, and immunity, platelets play a critical role in the initiation and progression of sepsis. Beyond their traditional function in hemostasis, platelets actively participate in immune modulation, inflammatory amplification, and immunothrombosis. This review systematically summarizes the molecular and cellular mechanisms through which platelets contribute to organ injury in sepsis, with particular emphasis on platelet-immune cell interactions. We discuss how these processes drive the development of acute lung injury, myocardial depression, hepatic and renal dysfunction, and disseminated intravascular coagulation. In addition, we examine the dynamic alterations in platelet phenotype and function during sepsis and their clinical implications. Ultimately, we evaluate the therapeutic potential of antiplatelet strategies, addressing current challenges and future directions for translating platelet-targeted interventions into effective treatments for sepsis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IqgD is a Rac1-interacting IQGAP required for efficient growth of Dictyostelium discoideum on bacterial lawns.","authors":"Anja Čizmar, Darija Putar, Marija Šimić, Jonas Scholz, Maja Marinović, Lucija Horvat, Mihaela Matovina, Igor Weber, Jan Faix, Vedrana Filić","doi":"10.1186/s12964-026-03074-w","DOIUrl":"10.1186/s12964-026-03074-w","url":null,"abstract":"<p><strong>Background: </strong>Phagocytosis of surface-bound microbes is essential for host defence and environmental feeding, yet the mechanism by which macrophages remove surface-bound particles has only recently been described. This process involves the formation of an F-actin-rich, force-bearing ring around the surface-attached particle. Here, we identify the IQGAP-related protein IqgD from the professional phagocyte Dictyostelium discoideum as a key regulator of mechanically demanding phagocytosis. IQGAPs are large multidomain scaffold proteins that interact with Rho family GTPases and F-actin. IqgD contains a calponin homology domain (CHD), a GAP-related domain (GRD), a RasGAP C-terminal (RGCT), and an extreme C-terminal (CT) domain.</p><p><strong>Methods: </strong>In this study, we used biochemical and imaging approaches with full-length and truncated protein variants to investigate whether IqgD interacts with D. discoideum Rho GTPases and F-actin. We also performed comprehensive phenotypic characterisation of IqgD-deficient cells to determine the cellular function of IqgD.</p><p><strong>Results: </strong>We show that the CHD is essential for F-actin binding and cortical localisation, while the GRD and CT domains mediate interactions with Rac1 GTPases and the actin-bundling proteins cortexillins. Moreover, similar to mammalian IQGAPs, IqgD maintains Rac1 in its active conformation. Although IqgD is enriched in macropinocytic and phagocytic cups, it is not required for fluid uptake or internalisation of bacteria from suspension. However, loss of IqgD markedly reduces growth on bacterial lawns and strongly impairs uptake of surface-attached microbeads and yeast particles. Furthermore, IqgD localises to F-actin-rich ring-like structures that form around surface-bound particles at the basal cell surface.</p><p><strong>Conclusions: </strong>IqgD is not required for all forms of macroendocytosis; rather, it is specifically required for mechanically demanding phagocytosis. This includes the formation of enlarged phagocytic cups during phagocytosis of yeast particles or the generation of greater force, as in phagocytosis of surface-bound particles and bacteria within bacterial lawns. Similar to phagocytosis of surface-attached particles in mammalian macrophages, D. discoideum also forms an F-actin-rich ring around the particle at the cell base, suggesting that force-driven particle detachment and internalisation may be an evolutionarily conserved mode of substrate-dependent phagocytosis. Our findings provide mechanistic insight linking IqgD with Rac1, cortexillins, and F-actin in the regulation of demanding forms of phagocytosis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.","authors":"Myungjin Jo, Seyeon Kim, Junghwa Woo, Jin-Sung Park, Seung Hyun Kim, Minyeop Nahm, Sang Ryong Kim, Shinrye Lee, Hyung-Jun Kim","doi":"10.1186/s12964-026-03082-w","DOIUrl":"10.1186/s12964-026-03082-w","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders characterized by reactive astrocytes that contribute to neuronal injury through TAR DNA-binding protein 43 (TDP-43)-or fused in sarcoma (FUS)-driven neuroinflammatory signaling. Dehydrocostus lactone (DHE), a blood-brain barrier-permeable sesquiterpene lactone with established anti-inflammatory activity, represents a promising but unexplored therapeutic candidate for ALS/FTD.</p><p><strong>Methods: </strong>The therapeutic effects of DHE were evaluated in primary mouse and human astrocytes expressing ALS/FTD-associated RNA-binding protein pathology, ALS patient-derived fibroblasts, and primary cortical neurons exposed to astrocyte-conditioned medium. Drosophila models expressing mutant FUS or TDP-43 in glial cells were used to assess locomotor performance and survival. Molecular analyses examined nuclear factor kappa B (NF-κB) signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant responses, protein aggregation, mitochondrial function, and inflammatory mediator production. Plasma concentrations of inflammatory cytokines and chemokines were measured in patients with sporadic ALS.</p><p><strong>Results: </strong>DHE exerted neuroprotective effects through a dual mechanism involving suppression of NF-κB-dependent inflammatory signaling and activation of NRF2-mediated antioxidant pathways in astrocytes exhibiting FUS or TDP-43 proteinopathy. DHE attenuated astrocyte-mediated neurotoxicity and improved neuronal mitochondrial function in conditioned-medium assays. In addition, DHE reduced pathological FUS accumulation in FUS P525L-expressing astrocytes and in stress-challenged patient-derived fibroblasts. In Drosophila models, DHE significantly improved locomotor function and extended survival. Translationally, the chemokines CXCL10, CCL3, and CCL19 were elevated in plasma from patients with ALS, were induced by FUS or TDP-43 pathology in astrocytes, and were suppressed by DHE treatment, supporting the clinical relevance of the inflammatory pathways targeted by DHE.</p><p><strong>Conclusion: </strong>DHE mitigates astrocyte-driven neurotoxicity associated with ALS/FTD-related RNA-binding protein pathology by suppressing inflammatory signaling and enhancing antioxidant defense mechanisms. The consistent therapeutic effects observed across mouse and human cellular models, patient-derived samples, and in vivo Drosophila models support further investigation of DHE as a potential therapeutic strategy for ALS/FTD and highlight astrocyte-mediated signaling pathways as actionable targets in neurodegenerative disease.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM47 catalyzes MAVS SUMOylation to safeguard chronic viral infections and tissue inflammation.","authors":"Wenting Lu, Junji Xing, Junying Wang, Laurie J Minze, Xian C Li, Zhiqiang Zhang","doi":"10.1186/s12964-026-03066-w","DOIUrl":"10.1186/s12964-026-03066-w","url":null,"abstract":"<p><strong>Background: </strong>Chronic tissue inflammation causes progressive tissue damage, organ dysfunction, and increased susceptibility to inflammatory diseases. Viral infections are major drivers of this process, but the molecular mechanisms linking antiviral immune responses to persistent inflammation and tissue pathology remain poorly understood.</p><p><strong>Methods: </strong>The function of TRIM47 was examined using primary macrophages and mouse models of RNA virus infection. Alveolar macrophages, peritoneal macrophages, and bone marrow-derived macrophages (BMDM) from wild-type and Trim47-deficient (Trim47-KO) mice were treated with RNA viruses or RNA mimics, and antiviral cytokine production was quantified. Sublethal reovirus and influenza A virus infection mouse models were used to evaluate survival, cytokine responses, and viral titers in vivo. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to identify TRIM47-interacting proteins. Molecular and biochemical assays were used to examine post-translational modification, aggregation and activation of mitochondrial antiviral-signaling protein (MAVS).</p><p><strong>Results: </strong>TRIM47 was highly expressed in macrophages, and TRIM47 deficiency in BMDM markedly reduced type I interferon (IFN-I) production following RNA virus infection or RNA mimics stimulation. In sublethal RNA virus infection mouse models, Trim47-KO mice exhibited reduced survival, impaired IFN-I responses, higher viral titers, increased inflammatory cell infiltration and tissue inflammation including myocarditis compared to wild-type mice. Mechanistically, TRIM47 interacted with MAVS and promoted SUMO1-mediated MAVS SUMOylation at K297 and K348, thereby enhancing MAVS aggregation and activation and driving robust IFN-I, IL-1β and IL-18 production in macrophages.</p><p><strong>Conclusions: </strong>These findings establish TRIM47 as a molecular switch of MAVS activation and antiviral cytokine responses in macrophages, highlighting its role in restricting RNA virus infection and mitigating inflammation. This study provides mechanistic insight into host pathways that may be therapeutically leveraged in chronic viral inflammation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-driven multi-omics deciphering of extrachromosomal circular DNA rescues hidden targets in colorectal cancer.","authors":"Lili Zhang, Jian Cui, Tianhan Sun, Chang Li, Xuanmei Luo, Jinxin Shi, Gaoyuan Sun, Gang Zhao, Wei Zhang, Fei Xiao","doi":"10.1186/s12964-026-03063-z","DOIUrl":"10.1186/s12964-026-03063-z","url":null,"abstract":"<p><strong>Background: </strong>Extrachromosomal circular DNA (eccDNA) is an emerging tumor biomarker notable for its tumor-specific amplification and contribution to genomic heterogeneity. However, the substantial heterogeneity of eccDNAs poses a significant challenge for characterization. Current identification tools rely predominantly on single data types, overlooking the integrative potential of multi-omics layers and often discarding sparse but biologically meaningful signals.</p><p><strong>Methods: </strong>To address this, we developed eccDNAOmix, an AI-empowered framework that integrates a specialized eccDNA sequencing pipeline with multi-omics data to evaluate the relative contributions of different biological modalities. Basing matched tumor and adjacent normal tissues from colorectal cancer patients, eccDNAOmix employs a masking strategy to eliminate non-biological noise and features a multimodal deep learning model with an adaptive gated fusion mechanism.</p><p><strong>Results: </strong>Our model achieved robust identification performance (AUC = 0.844), with the DNA sequence modality (AUC = 0.822) being the most identifiable feature for eccDNA identification. Leveraging this finding, we established a web server to facilitate practical eccDNA identification. Biological characterization showed that eccDNAs are preferentially derived from promoter regions and exhibit a significant enrichment of RNA modifications within 100 bp downstream of junction sites. Notably, eccDNAOmix rescued hidden eccDNA fragments from conventionally discarded unmapped sequencing reads and this was confirmed via experimental validation.</p><p><strong>Conclusions: </strong>By integrating multi-omics sequencing and eccDNA sequencing, this study provides the first comprehensive characterization of eccDNAs. Our multi-omics analysis demonstrates that the DNA sequence contributes the highest proportion to eccDNA identification. By leveraging this dominant identifiable role and providing an accessible single-modality identification tool, our work proposes a practical computational framework for advancing discovery in colorectal cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trophoblast cells rewire the epigenetic landscape of vascular smooth muscle cells to modulate plasticity: a regulatory axis disrupted in intrauterine growth restriction.","authors":"Poulomi Sarkar, Rupasri Ain","doi":"10.1186/s12964-026-03042-4","DOIUrl":"10.1186/s12964-026-03042-4","url":null,"abstract":"<p><strong>Background: </strong>Uterine spiral artery remodelling (SAR) is a fundamental developmental process that facilitates optimal placental perfusion and supports fetal growth. Central to SAR is the phenotypic transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state, directed by invasive trophoblast cells. To advance these findings, we sought to elucidate the epigenetic mechanisms governing trophoblast-induced reprogramming of VSMC identity, enabling plasticity required for uterine vascular adaptation.</p><p><strong>Methods: </strong>VSMC dedifferentiation was assessed by qRT-PCR, Western blotting, and immunofluorescence. Epigenetic alterations were evaluated by Western blotting. A chromatin remodelling PCR array was performed and validated by qRT-PCR and Western blotting. Chromatin remodelling factors were downregulated using antisense oligonucleotides (ASOs), and VSMC dedifferentiation was confirmed by Western blotting. E13.5 and E16.5 rat metrial glands were used for in vivo validation. An IUGR rat model was generated by administering dexamethasone from E13.5 to E20.5. In IUGR tissues, trophoblast invasion, VSMC dedifferentiation, and chromatin remodelling factor expression were validated by Western blotting.</p><p><strong>Results: </strong>Co-culture of primary E16.5 rat trophoblast cells with VSMCs revealed a trophoblast-induced shift in the expression landscape of epigenetic regulators, resulting in upregulation of chromatin-modifying \"writers\" (CBP, DNMT1, DNMT3A), downregulation of \"erasers\" (HDAC 1,2,3), and an increase in both transcription activation marks (H3K27ac, H3K9ac) and repression marks (H3K27me3, H3K9me3). Targeted real-time PCR array profiling identified coordinated downregulation of 13 chromatin remodelling genes (ARID1B, SMARCAD1, SMARCD1, SMARCD3, BMI1, EZH2, CBX2, CBX5, CBX6, BAZ1B, ZMYND8, CHD1, MBD3,) during VSMC de-differentiation. This change in the epigenetic landscape was recapitulated in vivo within the metrial gland, the entry point of uterine spiral arteries, on E16.5. Knockdown of these factors impaired the phenotypic transition of VSMCs, establishing their mechanistic role in enabling vascular adaptation. Notably, in a model of intrauterine growth restriction (IUGR), the normal expression dynamics of chromatin remodelling factors and VSMC phenotypic markers were reversed, indicating the need for the dynamic epigenetic regulatory axis, which is essential for vascular adaptation in healthy pregnancies.</p><p><strong>Conclusions: </strong>These findings uncover a trophoblast-driven epigenetic axis that governs VSMC plasticity during SAR and highlight its dysregulation as a potential contributor to the pathogenesis of IUGR.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}