Cell Communication and Signaling最新文献

{"title":"Resveratrol attenuates diabetic RGC degeneration through TRIM23-dependent VDAC1 ubiquitination and mitophagy.","authors":"Ruohong Wang, Xiaohong Ma, Zheng Zhong, Jiaqi Li, Yunxi Ma, Huimin Yu, Yuhe Tan, Lei Ruan, Yin Zhao, Xufang Sun","doi":"10.1186/s12964-026-03105-6","DOIUrl":"10.1186/s12964-026-03105-6","url":null,"abstract":"<p><strong>Background: </strong>Retinal ganglion cells (RGCs) degeneration is an early event in diabetic retinopathy (DR), tightly coupled to mitochondrial dysfunction. While the mitochondrial gatekeeper voltage-dependent anion channel 1(VDAC1) is a known mediator of apoptosis, its regulation and therapeutic targeting in diabetic RGCs remain unclear.</p><p><strong>Methods: </strong>We examined VDAC1 expression in human donor retinas, streptozotocin-induced diabetic mice, and high glucose-treated SH-SY5Y cells. VDAC1-knockdown SH-SY5Y cells were established to explore its functional role in the context. Using virtual screening and molecular docking, we identified resveratrol (RSV) as a potential VDAC1 inhibitor, which was further validated by surface plasmon resonance binding assays and RSV-based pull-down experiments. The effects of RSV were assessed by RGCs survival, retinal electrophysiological function, and mitochondrial quality control. Tripartite motif-containing 23 (TRIM23)-VDAC1 interaction along with ubiquitination modifications were confirmed by co-immunoprecipitation. Finally, combination therapy involving RSV and adeno-associated virus serotype 2 (AAV2) carrying the γ-synuclein (SNCG) promoter mediated Trim23 overexpression was applied in both DR and acute ocular hypertension (AOH) animal models.</p><p><strong>Results: </strong>VDAC1 was upregulated in diabetic RGCs, and its knockdown was protective. We further discovered that RSV recruits the E3 ligase TRIM23 to VDAC1, inducing a K27-linked ubiquitination switch that promotes mitophagy instead of apoptosis. We propose that RSV binding acts as an allosteric switch, reconfiguring VDAC1 to favor this protective ubiquitination pathway. Consequently, RSV restored mitochondrial health and RGCs viability. Therapeutically, enhancing this axis via RSV and RGCs-targeted Trim23 overexpression synergistically protected against RGCs loss in both DR and AOH models.</p><p><strong>Conclusion: </strong>Our study unveils a pharmacologically inducible switch wherein RSV, via direct VDAC1 binding, redirects its function toward TRIM23-mediated K27-linked ubiquitination and mitophagy. The TRIM23-VDAC1 allosteric axis represents a novel therapeutic paradigm for neuroprotective intervention in DR and beyond.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042168","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":"Gonad-soma inter-tissue communication alleviates ultraviolet-induced neurotoxicity in C. elegans.","authors":"Wenjing Zhang, Liu Ding, Shanpeng Qiao, Jiyu Xu, Qiyi Yi, Binmei Liu, Po Bian, Ting Wang","doi":"10.1186/s12964-026-03095-5","DOIUrl":"10.1186/s12964-026-03095-5","url":null,"abstract":"<p><p>Organismal genome stability is constantly challenged by endogenous and exogenous genotoxins, and DNA damage response (DDR) is a classical cell-autonomous mechanism for counteracting such damage. It remains unclear how somatic cells with DDR deficiencies maintain genomic integrity under stress. This study investigated whether inter-tissue communication, particularly from the reproductive system, coordinates DNA damage repair in repair-deficient cells. Using Caenorhabditis elegans, in which certain upstream DDR signaling components are transcriptionally repressed in somatic cells, we examined UV-induced neurotoxicity through behavioral assays (head thrashes, body bends, foraging, and salt chemotaxis). These deficits were associated with preferential impairment of dopaminergic, glutamatergic, and serotonergic reporter readouts, along with heterogeneous transcriptional remodeling of neurotransmitter pathway and pan-neuronal synaptic genes. Deficiencies in upstream DDR signaling (ATM/ATR), whether systemic or germline-specific, significantly exacerbated UV-induced neurobehavioral and transcriptional deficits. In contrast, germline-specific loss of nucleotide excision repair (NER) machinery had no significant effect, highlighting a unique inter-tissue signaling role for upstream DDR. Furthermore, CPR-4 was identified as a key mediator of this inter gonad-soma signaling. Germline DDR activation regulated cpr-4 expression, and loss of CPR-4 abolished UV-induced transcriptional activation of the somatic NER pathway and heightened behavioral sensitivity. Our study revealed a novel germline DDR to somatic tissue signaling axis essential for organismal stress resilience and proposed a new regulatory model centered on gonad-soma signaling.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225444","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":"SFPQ/S100A8 complex induces filaggrin deficiency via selective autophagy and JNK phosphorylation in atopic dermatitis.","authors":"Geunyeong Kim, Yujin Hong, Tae Young Han, Byeol Han, Beom Seok Park, Eun Ju Yang, Ayesha Kashif, Young Joon Jun, Hongchan An, Juram Lee, Ji Sook Lee, In Sik Kim","doi":"10.1186/s12964-026-02776-5","DOIUrl":"10.1186/s12964-026-02776-5","url":null,"abstract":"<p><strong>Background: </strong>Although atopic dermatitis (AD) is associated with a decrease of filaggrin levels, the underlying mechanisms are not clearly understood. Here, we aimed to investigate the pathogenic roles of the splicing factor proline- and glutamine-rich (SFPQ)/S100 calcium-binding protein A8 (S100A8) complex, a critical regulator inducing filaggrin deficiency in AD.</p><p><strong>Methods: </strong>The formation of SFPQ/S100A8 complex was analyzed in the keratinocytes and skin tissues from patients with AD and 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice. The effects of leptomycin B, a CRM1 inhibitor, and rapamycin, a mTOR inhibitor were determined in DNCB-induced AD-like mice and the non-lesional and lesional primary keratinocytes of AD patients.</p><p><strong>Results: </strong>The relocation of SFPQ from the nucleus to the cytoplasm, elevated S100A8 levels, and SFPQ/S100A8 complex formation were proportional to filaggrin deficiency and AD severity in the keratinocytes of AD patients and AD-like mice. Interaction of the complex with filaggrin and c-Jun N-terminal kinase (JNK) accelerated filaggrin degradation via selective autophagy and filaggrin downregulation via JNK phosphorylation, respectively. The mechanistic target of rapamycin kinase (mTOR) and chromosomal region maintenance 1 (CRM1) facilitated the cytosolic export of SFPQ to form the complex in human keratinocytes. Administration of leptomycin B and rapamycin suppressed the decrease in filaggrin levels by inhibiting SFPQ/S100A8 complex formation in AD-like mice.</p><p><strong>Conclusions: </strong>This study demonstrates that the formation of SFPQ/S100A8 complex is a critical process in AD progression, which provides key insights into the pathogenic mechanisms of AD. The elucidation of the SFPQ/S100A8 complex axis in AD pathogenesis can be leveraged to develop therapeutic drugs for AD treatment.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225499","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 mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.","authors":"Reza Mansouri, Claudia Alcedo, Adriana Gavino-Dias, Antonio Muro, Raúl Manzano-Román, Sajad Rashidi","doi":"10.1186/s12964-026-03099-1","DOIUrl":"10.1186/s12964-026-03099-1","url":null,"abstract":"<p><p>The interplay between metabolic pathways and immune responses is critical for understanding host-parasite interactions in protozoan infections. This review examines the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways-key routes for isoprenoid synthesis essential for sterol production and bioactive compounds. Beyond sustaining parasite survival, these pathways directly influence host immune signaling cascades, including NF-κB, MAPK, PI3K/Akt, and mTOR. A critical conceptual distinction is introduced: genuine \"moonlighting\" functions-where a single enzyme performs two distinct molecular roles-are currently documented only for mevalonate kinase in trypanosomatids. Leishmania donovani secretes mevalonate kinase (LdMVK), which has been associated with modulation of macrophage inflammatory signaling and attenuation of NF-κB-dependent cytokine responses. Similarly, Trypanosoma cruzi mevalonate kinase (TcMVK) alters host calcium signaling and MAPK activation, promoting parasite invasion. By contrast, most effects described in the literature-such as trained immunity induction or Th1/Th2 skewing following statin treatment-represent pleiotropic consequences of canonical pathway disruption. Therapeutically, the absence of the MEP pathway in humans and structural divergence of parasitic MVA enzymes enable selective targeting. Strategies include drug repurposing (statins, bisphosphonates), novel enzyme inhibitors, and immunomodulatory approaches. However, parasitic metabolic plasticity and host toxicity remain challenges, supporting \"double-hit\" combination therapies that simultaneously disrupt parasite metabolism and block salvage pathways to overcome resistance. By integrating metabolic essentiality with immune signaling, MVA/MEP pathways emerge as multifunctional hubs offering promising avenues for precision therapies and vaccines against neglected tropical diseases.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208107","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":"AKAP2/PKA complex coordinates primary ciliogenesis, ciliary trafficking and Shh signaling.","authors":"Francesco Chiuso, Giuliana Giamundo, Emanuela Senatore, Laura Rinaldi, Francesca Rizzo, Simona Aversano, Antonio Giuseppe Bianco, Alfonso Carleo, Elena Alexandrova, Alessandro Weisz, Jack Brendan Jordan, Iolanda Carratù, Stephane Audebert, Luc Camoin, Maria Chiara Zizolfi, Leandra Sepe, Paolo Maiuri, Luca Lignitto, Ivan Conte, Antonio Feliciello","doi":"10.1186/s12964-026-03092-8","DOIUrl":"10.1186/s12964-026-03092-8","url":null,"abstract":"<p><p>The primary cilium is a sensory organelle present in all eukaryotic cells that acts as a signaling hub that receives, integrates and transmits signals carried out by extracellular stimuli, playing a fundamental role in cell behavior, development and tissue homeostasis. Genetic mutations in genes encoding for structural components and regulators of primary cilium underlie severe developmental defects, also known as ciliopathies. Understanding cilium biology may, thus, provide novel therapeutic strategies for ciliopathies. Here, we report that A-Kinase Anchor protein 2(AKAP2) dynamically localizes within the primary cilium and forms complexes with kinesin motor proteins and components of the intra-flagellar transport system. Genetic deletion experiments and functional analysis demonstrate that AKAP2/PKA complex controls cilium biogenesis and intraciliary trafficking of cargo receptors, acting as a positive regulator of Shh pathway. In the medaka fish model, depletion of AKAP2 affects ciliogenesis and ciliary trafficking, delays embryonic development and significantly increases the embryonic death rate.Our findings identify AKAP2 as a ciliary scaffold protein that finely controls ciliogenesis, intraciliary trafficking and Hedgehog signaling cascade. Manipulating ciliary AKAP2 signaling, thus, provides a new therapeutic window for ciliopathy disorders.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225506","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":"DRP1 lysine 616 lactylation exacerbates cerebral ischemia-reperfusion injury by activating the STING inflammatory pathway.","authors":"Xiaoqi Ma, Dan Xin, Xianjia Li, Zhenhao Ying, Zifeng Li, Wenli Wang, Zhigang Mei, Jinwen Ge","doi":"10.1186/s12964-026-03093-7","DOIUrl":"10.1186/s12964-026-03093-7","url":null,"abstract":"<p><p>Ischemia-hypoxia-induced inflammation and glycolysis are linked to the severity of cerebral ischemia-reperfusion injury (CIRI), but the mechanisms are unclear. Current research suggests that the inflammatory response of immune cells activated by STING is a key regulatory molecule in cellular inflammatory damage. However, the specific mechanisms underlying STING-mediated CIRI inflammatory responses remain unclear. This study found that STING expression was specifically elevated in microglia in the damaged side of the hippocampus in CIRI model mice, and this elevation was positively correlated with the severity of CIRI. Our previous research indicated that the dynamic process of mitochondrial fusion and fission is closely associated with CIRI. Building on this, we integrated glycolysis, mitochondrial fission, and the STING inflammatory pathway. Mechanistically, our data suggest that DRP1 K616 is a critical candidate site involved in DRP1 lactylation-associated regulation, which promotes STING pathway activation and contributes to the progression of CIRI. In conclusion, our findings offer substantial evidence that lactate-driven DRP1-mediated mitochondrial fission facilitates the involvement of the STING inflammatory pathway in CIRI. These results suggest that modulating lactate metabolism may serve as a crucial upstream strategy for therapeutic intervention in CIRI.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551174","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":"Dying cells initiate DLL4-Notch signaling to drive tumor repopulation after insufficient thermal ablation of papillary thyroid carcinoma.","authors":"Yongchao Yu, Weichao Chen, Zan Jiao, Kang Ning, Taonong Cai, Bu Zou, Honghao Deng, Tong Wu, Zhongyuan Yang, Feng Han, Ankui Yang, Mingjie Jiang","doi":"10.1186/s12964-026-03106-5","DOIUrl":"10.1186/s12964-026-03106-5","url":null,"abstract":"<p><strong>Background: </strong>Although lacking high-quality clinical evidence, the use of thermal ablation for papillary thyroid carcinoma (PTC) is increasing. Emerging evidence suggests that thermal ablation may accelerate tumor progression in some patients, but the underlying biological mechanisms remain unclear. This study aims to explore the mechanisms of tumor repopulation following thermal ablation and identify possible intervention strategies.</p><p><strong>Materials and methods: </strong>In vitro and in vivo models were employed to simulate tumor repopulation after thermal ablation and investigate mechanisms. Clinicopathological features of post-ablation surgical specimens were analyzed, and Xenium in situ spatial transcriptomics was conducted. Time-lapse imaging and RNA-seq explored how dying cells influence surviving cells. qPCR, WB, IHC, and flow cytometry validated molecular mechanisms, while enChIP-MS identified upstream regulators.</p><p><strong>Results: </strong>Post-ablation PTC tissue showed significantly higher proliferative potential. Heat-induced dying cells promote surviving cell repopulation in a contact-dependent manner. Dying cells upregulated DLL4, activating Notch signaling in surviving cells and driving proliferation. Clinical specimens and Xenium in situ spatial transcriptomics revealed elevated Notch activity in tumor cells adjacent to the ablation bed. Inhibition of DLL4-Notch signaling attenuated the dying cell-induced proliferative advantage in vitro and in vivo. enChIP-MS showed HNRNPU enrichment at the DLL4 promoter after heat treatment. Mechanistically, heat treatment increased HNRNPU nuclear enrichment and binding at the DLL4 promoter, facilitating DLL4 transcription.</p><p><strong>Conclusion: </strong>Heat-induced dying cells promote tumor repopulation after insufficient thermal ablation in PTC through the DLL4-Notch pathway. With the expanding use of thermal ablation, understanding and mitigating its limitations is essential for clinical advancement.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208090","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":"Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.","authors":"Neha Kaushik, Soumya Rastogi, Vaibhav Jain, Sonia Verma, Deepak Pandey, Mona Sharma, Ashutosh Halder, Simon Gregory, Neeraj Kumar","doi":"10.1186/s12964-026-03069-7","DOIUrl":"10.1186/s12964-026-03069-7","url":null,"abstract":"<p><strong>Background: </strong>The somatic gonad plays a central role in supporting germline development and maintaining oocyte and embryonic integrity, both of which are essential for sustained reproductive function. With age, deterioration of somatic gonadal structures compromises germline support, leading to declines in oocyte morphology and increased embryonic abnormalities. The insulin/IGF-1 signaling (IIS) pathway regulates longevity and reproductive aging, and its reduction (rIIS) in the daf-2(e1370) mutant extends reproductive span in Caenorhabditis elegans. While prior work has largely focused on germline stem cells and oocyte maturation, the molecular mechanisms by which IIS preserves somatic gonadal architecture and thereby maintains oocyte and embryonic morphological integrity remain poorly understood. Elucidating how reduced IIS influences the somatic gonad can provide insights into the coordination of systemic aging pathways with tissue-specific mechanisms that sustain reproductive health.</p><p><strong>Methods: </strong>We identified somatic gonad-enriched genes from temporal transcriptomic datasets of reduced IIS animals, highlighting collagens consistently upregulated with age. Using RNAi knockdowns in both systemic and somatic gonad-specific RNAi-sensitive strains of Caenorhabditis elegans, we examined effects on self-reproductive span, oocyte and embryonic morphology, and somatic gonad integrity. Age-associated morphological changes were assessed by differential interference contrast microscopy, and regulatory dependencies were tested via quantitative polymerase chain reaction following knockdown of key transcription factors.</p><p><strong>Results: </strong>Several collagens were found to be essential for maintaining somatic gonadal architecture and preserving oocyte morphology during aging. Gonad-specific knockdown of these collagens caused structural deterioration, impaired oocyte and embryo quality, and accelerated reproductive decline. These defects occurred without a major reduction in total progeny number, suggesting that age-related reproductive loss arises primarily from tissue deterioration rather than immediate fertility impairment. Expression and function of these collagens were largely dependent on key transcription factors downstream of IIS.</p><p><strong>Conclusion: </strong>Our findings uncover a previously unrecognized role for somatic gonadal collagens in preserving reproductive function under IIS. By maintaining gonadal architecture and sustaining oocyte and embryonic morphological integrity, these collagens act as downstream effectors of IIS-mediated reproductive longevity. Targeting gonadal collagen networks may therefore represent a potential strategy to mitigate age-related reproductive decline and warrants further investigation in higher-order models.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221179","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":"Oligonucleotide G3T19 downregulates CD44 succinylation and inhibits astrocyte-induced glioma immune escape.","authors":"Xiaoming Sun, Xinyu Wang, Saijun Zhang, Ying Long, Danni Wang, Changlong Gou, Wenzi Zhang, Chunlei Deng, Cui Liu, Zhuo Chen","doi":"10.1186/s12964-026-03081-x","DOIUrl":"10.1186/s12964-026-03081-x","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes (ACs) play a crucial role within the immune microenvironment of glioma, facilitating its progression. Protein succinylation, a post-translational modification, may serve as a significant regulatory mechanism. SsDNA (single-chain oligonucleotide) drugs with specific sequences for the treatment of tumors have entered clinical trials with remarkable effects.</p><p><strong>Methods: </strong>G3T19 was evaluated by peroxidase-like activity assay and circular dichroism experiments. The effects of G3T19 on glioma were evaluated by flow cytometry, CCK-8, transwell migration assay, immunohistochemistry, small animal imaging, HPLC, orthotopic xenograft glioma model and human glioma organoid model. The binding of G3T19 and CD44 was examined by immunoprecipitation assay, ELONA assay, immunofluorescence, and docking conformation visualization. The effect of G3T19 on CD44 succinylation was evaluated by mass spectrometry analysis, immunoprecipitation assay, and flow cytometry.</p><p><strong>Results: </strong>G3T19 with G-quadruplex parallel structure binds to CD44 and inhibits AC-enhanced glioma immune escape. CD44 succinylation in ACs adjacent to gliomas is enhanced at lysine 40; however, G3T19 reduces CD44 succinylation to inhibit AC-enhanced glioma immune escape. G3T19-dependent targeting of CD44 reduces NF-κB signaling, PD-L1 expression, and AC-induced glioma immune escape.</p><p><strong>Conclusion: </strong>These results confirm that G3T19 binds CD44 and downregulates CD44 succinylation, inhibits NF-κB pathway and the expression of PD-L1, inhibits AC-induced glioma immune escape. This study identifies a new anti-tumor mechanism based on the advanced structure of a functional nucleic acid that may be useful in the development of drugs for glioma immunotherapy.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551105","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":"Mesenchymal WNT signaling coordinates epithelial and mesenchymal differentiation in the developing murine ureter.","authors":"Mark-Oliver Trowe, Philipp Straube, Florian Bergmann, Nurullah Aydogdu, Hauke Thiesler, Herbert Hildebrandt, Tobias Bohnenpoll, Andreas Kispert","doi":"10.1186/s12964-026-03094-6","DOIUrl":"10.1186/s12964-026-03094-6","url":null,"abstract":"<p><strong>Background: </strong>The coordinated development of the mesenchymal and epithelial primordia of the murine ureter requires intense tissue communication. Previous studies have revealed the crucial role of the FGFR2-SHH-FOXF1-BMP4 signaling axis in the proliferation and differentiation programs of both the epithelium and the mesenchyme. Canonical (β-Catenin/CTNNB1-dependent) WNT signaling in the mesenchymal primordium has been reported to influence mesenchymal development by enhancing proliferation and favoring the smooth muscle cell fate over adventitial fibrocytes.</p><p><strong>Methods: </strong>To investigate the role of mesenchymal WNT signaling in early ureter development further, we analyzed the ureters of Ctnnb1-deficient mouse mutants for cellular and molecular changes during embryogenesis. Using pharmacological inhibition and activation approaches in explant cultures of embryonic ureters, we assessed the contribution of altered signaling activities to differentiation changes in Ctnnb1-deficient ureters. Transcriptional profiling of embryonic ureters with short-term WNT signaling inhibition allowed us to identify the primary targets of this signaling pathway in the ureteric mesenchyme.</p><p><strong>Results: </strong>We demonstrate that both mesenchymal and epithelial differentiation are impaired in ureters lacking mesenchymal Ctnnb1. This defect is linked to an inability to activate pro-differentiation transcription factors in either tissue primordia. Epithelial changes can be attributed, at least in part, to the loss of BMP4 signaling and the gain of canonical WNT signaling in the epithelial primordium. Mesenchymal WNT signaling directly activates transcription of multiple components of the SHH-FOXF1-BMP4 signaling axis, thereby enhancing this module in the inner region of the ureteric mesenchyme.</p><p><strong>Conclusions: </strong>Our work improves the understanding of the signaling network that coordinates cytodifferentiation in the early ureter. Mesenchymal WNT signaling plays a central role in mesenchymal fate decisions but also in promoting epithelial differentiation through enhancement of the SHH-FOXF1-BMP4 axis and inhibition of epithelial WNT-signaling.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551103","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}