Cell Communication and Signaling最新文献

{"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}

{"title":"Correction: Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.","authors":"Jinxin Lu, Xiaoyu Zhang, Keyu Su, Huandong Luo, Congcong Liu, Yuqing Yang, Bin He, Cenxin Wang, Zhuoran Zhao, Xianxian Liu, Xu Wang, Peixuan Meng, Dekang Lv, Chunli Wang, Keith W Kelley, Ling Wang, Bai Cui, Quentin Liu, Fei Peng","doi":"10.1186/s12964-026-03056-y","DOIUrl":"10.1186/s12964-026-03056-y","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457741","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":"TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.","authors":"Haixia Wang, Ruiming Wen, Emily Parker, Luodan Yang","doi":"10.1186/s12964-026-03083-9","DOIUrl":"10.1186/s12964-026-03083-9","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells 2 (TREM2) is a critical myeloid receptor expressed on the surface of central nervous system microglia, capable of integrating signals from lipids, damage-associated molecular patterns, and abnormal protein aggregates to regulate phagocytosis, metabolic adaptation, inflammatory remodeling, and pathology-associated responses. Accumulating evidence indicates that TREM2 is neither uniformly protective nor uniformly pathogenic; rather, its biological effects are highly context-dependent, governed collectively by disease stage, pathological substrates, cellular compartments, and the local microenvironment. By coupling with TYROBP/DAP12 or DAP10, TREM2 actively drives the state remodeling of pathology-associated microglia. It profoundly influences the onset and progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), as well as acute central nervous system injuries, including ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). Concurrently, soluble TREM2 (sTREM2) holds significant potential not only as a biomarker but also as a context-dependent effector molecule actively participating in pathological regulation. This review synthesizes current advancements by focusing on four core themes: the structural and signaling logic of the TREM2 axis; its regulation of disease-associated microglia (DAM) remodeling; the cross-disease significance of sTREM2; and the mechanistic basis for the divergent outcomes observed with TREM2-targeted therapies across different experimental models and disease stages. The objective is to elucidate the context-dependent roles of TREM2 by analyzing consensus mechanisms, sources of discrepancy, and translational implications, thereby providing a theoretical framework and strategic direction for more precise TREM2-targeted interventions.</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/PMC13651156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457718","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":"IGF2R: a new player in the IGF2 loop sustaining adrenocortical carcinogenesis.","authors":"Emma Nozza, Emanuela Esposito, Sonia Di Bari, Rosa Catalano, Genesio Di Muro, Anna Maria Barbieri, Elisa Cassinotti, Serena Palmieri, Alessandra Mangone, Valentina Morelli, Mariangela Tamburello, Constanze Hantel, Laura-Sophie Landwehr, Guido Di Dalmazi, Emanuele Ferrante, Giovanna Mantovani, Erika Peverelli","doi":"10.1186/s12964-026-03057-x","DOIUrl":"10.1186/s12964-026-03057-x","url":null,"abstract":"<p><strong>Background: </strong>Most of adrenocortical carcinomas (ACC) are characterized by IGF2 overexpression; therefore, several studies have focused on its two oncogenic effectors, the tyrosine-kinase receptors IGF1R and IR. However, the specific IGF2 receptor, IGF2R, due to its scavenging activity, was considered a tumour suppressor and has never been fully investigated in this context. Nevertheless, recent evidence from other tumours identified IGF2R as a pro-tumorigenic actor able to exert its function through the downstream activation of the pro-mitotic sphingosine kinases (SphK) enzymes responsible for sphingosine phosphorylation. Hence, the main aims of this study were to elucidate the role of IGF2R in ACC cells, investigate its action mechanism, and test IGF2R and SphK inhibitors as possible novel therapies for ACC.</p><p><strong>Methods: </strong>The present study was conducted in vitro in 4 different ACC cell lines and in 3 ACC primary cultures, to reflect the heterogeneity of ACC. Target protein and transcript expression were evaluated on normal and tumoral adrenal tissues and cell lines, while the effects of IGF2R downregulation and overexpression, along with IGF2R and SphK inhibition, were tested on cell viability, proliferation, and apoptosis as well as cortisol secretion.</p><p><strong>Results: </strong>ACC tissue analysis demonstrated the IGF2R overexpression compared to normal adrenal cortex, which was also positively correlated with IGF2 and IGF1R expression in ACC. In vitro assays proved the pro-mitotic involvement of IGF2R and its role in the downstream activation of SphK. Finally, we observed the anti-tumoral efficacy of three different inhibitors of this pathway on ACC cell lines and primary cultures: a specific neutralizing anti-IGF2R antibody was tested for its anti-proliferative action, while two SphK inhibitors, safingol (SAF) and fingolimod (FTY), were able to decrease cell proliferation, viability, and cortisol secretion, while promoting cell apoptosis.</p><p><strong>Conclusions: </strong>Overall, this comprehensive in vitro evaluation of the role of IGF2R in ACC demonstrates its tumorigenic effect through SphK activation. Moreover, the three pharmacological strategies here employed successfully controlled in vitro ACC growth, suggesting IGF2R/SphK pathway represents a novel therapeutic target for ACC.</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/PMC13656604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457720","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":"Harnessing tumor-associated exosomal aminopeptidase N as a dual-function tool for monitoring and tackling chemoresistance in gastric cancer.","authors":"Wangyu Cai, Zheru Ma, Wen Xie, Ende Lin, Shengyuan Zheng, Lingyun Lin, Yuanyuan Xie, Zinan Dong, Peiyu Lv, Jia Cheng, Li Yang, Xiaoteng Fu, Fuxing Zhang, Zengpeng Li, Lin Wang","doi":"10.1186/s12964-026-03079-5","DOIUrl":"10.1186/s12964-026-03079-5","url":null,"abstract":"<p><p>Chemoresistance remains a major obstacle to effective treatment in gastric cancer (GC), with a notable scarcity of clinically applicable biomarkers and therapeutic targets. In this study, we employed an integrated proteomic approach analyzing paired serum samples from GC patients at disease control and progressive disease stages during chemotherapy, exosomes from chemoresistant and chemosensitive GC cells, and corresponding whole-cell proteomes to identify tumor-associated exosomal drivers of chemoresistance. Cross-dataset integration identified aminopeptidase N (APN/CD13) as selectively enriched under chemoresistant conditions. Functional validation demonstrated that APN depletion via shRNA or CRISPR restored cisplatin sensitivity in refractory cells, whereas APN overexpression conferred chemoprotection. A neutralizing anti-APN monoclonal antibody resensitized resistant cells and showed superior efficacy compared with the broad-spectrum peptidase inhibitor bestatin in vivo. Mechanistically, APN sustained a ferroptosis-suppressive state: its inhibition increased ROS and lipid peroxidation, shifted transcriptomic profiles toward pro-ferroptotic pathways, and downregulated the lipid peroxide detoxifier AKR1C2, which correlated with poor prognosis and APN expression in the TCGA-STAD cohort. Exosomal transfer assays confirmed that APN-enriched vesicles disseminated chemoresistance and ferroptosis evasion to sensitive cells, accelerating tumor progression during chemotherapy, whereas APN-deficient exosomes lacked this capacity. Clinically, serum exosomal APN levels robustly distinguished progressive disease from disease control in a cohort of 105 patients (AUC = 0.85; optimal cutoff 0.936 ng/mL). Collectively, these findings position exosomal APN as a dual-function tool, serving both as a dynamic liquid biopsy biomarker and an antibody-targetable node for monitoring and overcoming chemoresistance in gastric 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/PMC13651178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457729","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":"Parkinson's disease as a multi-axis systems disorder: integrating molecular pathology and circuit-level therapeutics.","authors":"Duc-Hiep Bach, Thanh Liem Nguyen","doi":"10.1186/s12964-026-03089-3","DOIUrl":"10.1186/s12964-026-03089-3","url":null,"abstract":"<p><p>Parkinson's disease (PD) has generated extensive mechanistic insight, yet nearly all candidate disease-modifying therapies have failed in clinical trials. Antibodies targeting α-synuclein, mitochondrial antioxidants, lysosomal interventions, and anti-inflammatory agents frequently achieve target engagement without slowing clinical progression, creating a central paradox in PD therapeutics.Here we propose that this discrepancy arises because PD is not primarily a single-pathway neurodegenerative disorder but a multi-scale systems disease. Molecular pathology, organellar dysfunction, immune activation, and large-scale network instability form a self-reinforcing cascade in which interventions acting at a single biological level cannot substantially modify disease once degeneration is embedded within distributed neural circuits.This framework generates testable predictions: pathway-targeted therapies may show benefit primarily in prodromal or biomarker-defined populations, whereas established clinical PD will likely require combination strategies coupling circuit restoration with axis-matched molecular interventions. Therapeutic responsiveness should therefore correlate more strongly with network integrity than with target engagement alone.Viewing PD as a multi-scale systems disorder provides a unifying explanation for repeated therapeutic failures and offers a framework for biomarker-guided, stage-matched disease-modifying trials.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450532","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":"Oncogenic PIK3CA reprograms glutamine metabolism to drive bladder cancer progression.","authors":"Karthik Reddy Kami Reddy, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Jun Hyoung Park, Aaditya Krishna Arun, Sachin B Jorvekar, Yongchao Dou, Mohammed Khurshidul Hassan, Chandra Sekhar Amara, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Jun Xu, Daniel Kraushaar, Adriana Langer Gramer, Allison C Bellman, Leomar Y Ballester, Yuan Xu, Robert Taylor Ripley, Seth P Lerner, Roni J Bollag, Martha K Terris, Chong-Xian Pan, Benny Abraham Kaipparettu, Yair Lotan, Nagireddy Putluri","doi":"10.1186/s12964-026-03058-w","DOIUrl":"10.1186/s12964-026-03058-w","url":null,"abstract":"<p><strong>Background: </strong>Genomic analysis has revealed that approximately 40% of bladder cancer (BLCA) tumors harbor alterations in the PI3K/AKT pathway, with PIK3CA mutations occurring in 15-25% of cases. PIK3CA, which encodes the catalytic p110α subunit of PI3K, plays a critical role in regulating cell survival, proliferation, and metabolism. However, the metabolic and functional consequences of PIK3CA mutations in BLCA remain poorly defined.</p><p><strong>Methods: </strong>To investigate the role of PIK3CA mutations in BLCA, we performed targeted sequencing on tumors from patients, identifying recurrent alterations. Using CRISPR/Cas9 knock-in models in SCaBER and UM-UC-3 cell lines, we introduced the PIK3CA E545K mutation to study its effects. We conducted transcriptomic profiling, targeted metabolomics, and stable isotope tracing to assess metabolic reprogramming. Functional assays measured proliferation, mitochondrial complex I activity, and glutaminolysis. Orthotopic xenografts in mice were used to evaluate in vivo tumor growth and metabolism.</p><p><strong>Results: </strong>PIK3CA mutations were present in 20% of cases, consistent with TCGA data. The E545K and E545Q hotspots accounted for 70% of these mutations. PIK3CA E545K strongly activated PI3K/AKT signaling. Transcriptomic analysis revealed enrichment of OXPHOS, fatty acid metabolism, and mTORC1 signaling. Metabolomics indicated changes in TCA cycle metabolites and enhanced reductive carboxylation of glutamine to citrate, driving fatty acid synthesis. Mutant cells showed increased expression of GLS1 and FASN, higher proliferation rates, and elevated mitochondrial complex I activity. In vivo, PIK3CA-mutant xenografts displayed significantly increased tumor growth.</p><p><strong>Conclusion: </strong>PIK3CA mutations are frequent drivers of metabolic reprogramming in BLCA, leading to increased glutamine flux, elevated OXPHOS activity, and enhanced fatty acid synthesis, all of which contribute to tumor progression. These findings provide the first comprehensive evidence that PIK3CA-driven metabolic alterations are both biomarkers of aggressive disease and actionable therapeutic targets. The efficacy of PI3Kα inhibition in combination with metabolic targets may support its potential in precision medicine for PIK3CA-mutant BLCA and highlights the value of integrating metabolic biomarkers into treatment strategies for advanced BLCA.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450571","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":"A ROS/HIF-1α/JMY signaling axis drives radiation-induced migration and invasion of neural progenitor cells.","authors":"Oriane Bergiers, Hayet Bensalah-Pigeon, Oscar Gitton-Quent, Karim Ben M'Barek, Mahasen Saati, Christine Granotier-Beckers, Olivier Etienne, Delphine Moison, Guillaume Piton, Didier Busso, Marie-Justine Guerquin, Jose R Pineda, François D Boussin, Laurent R Gauthier","doi":"10.1186/s12964-026-03025-5","DOIUrl":"https://doi.org/10.1186/s12964-026-03025-5","url":null,"abstract":"<p><strong>Background: </strong>Neural progenitor cell (NPC) migration is essential for proper cortical development, and its disruption contributes to severe brain malformations such as lissencephaly, polymicrogyria, and microcephaly. Although abnormal neuronal migration has been reported in irradiated embryos, the molecular mechanisms by which ionizing radiation affects NPC motility remain poorly understood.</p><p><strong>Methods: </strong>Fetal human and mouse NPCs were exposed to low doses of ionizing radiation (0.5-3 Gy). Migratory and invasive properties were assessed both in vitro and in vivo. Reactive oxygen species (ROS) production was monitored shortly after irradiation, and downstream signaling pathways were investigated through analysis of HIF-1α nuclear accumulation and expression of Junction-mediating and regulatory protein (JMY). Functional involvement of HIF-1α and JMY was tested using pharmacological or molecular inhibition approaches.</p><p><strong>Results: </strong>Ionizing radiation rapidly enhanced the migratory and invasive capacity of fetal human and mouse NPCs in vitro and in vivo. This response was preceded by an early increase in endogenous ROS, which initiated the migratory phenotype. Mechanistically, radiation-induced ROS promoted nuclear accumulation of HIF-1α, leading to upregulation of JMY, an actin nucleation-promoting factor that drives cytoskeletal remodeling and cell motility. Inhibition of either HIF-1α or JMY abolished the radiation-induced increase in NPC migration and invasion, identifying a conserved ROS/HIF-1α/JMY signaling axis as a key mediator of this effect.</p><p><strong>Conclusions: </strong>These findings reveal that low-dose ionizing radiation stimulates NPC migration and invasion through activation of a ROS/HIF-1α/JMY pathway. Given the critical requirement for tightly regulated NPC migration during brain morphogenesis, aberrant activation of this signaling axis may contribute to radiation-induced neurodevelopmental disorders.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450596","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}