Cell Communication and Signaling最新文献

{"title":"Phosphorylated IRF3 promotes GSDME-mediated pyroptosis through RIPK1/FADD/caspase-8 complex formation during mitotic arrest in ovarian cancer.","authors":"Wenjian Gong, Dongchen Zhou, Qiuyang Xu, Linghui Wang, Mengshi Luo, Yuewen Zhang, Zhiqi Liao, Fan Xiong, Guangnian Zhao, Bingbing Zhao, Qinglei Gao, Yong Fang","doi":"10.1186/s12964-025-02322-9","DOIUrl":"10.1186/s12964-025-02322-9","url":null,"abstract":"<p><p>Inducing mitotic arrest with anti-mitotic drugs is an effective strategy for cancer therapy. However, the ultimate fate of cells that undergo prolonged mitotic arrest remains largely uncertain. In this study, paclitaxel and nocodazole were used to induce prolonged mitotic arrest in ovarian cancer cells, triggering mitotic catastrophe, during which these cells exhibited hallmarks of pyroptosis. Subsequently, small interfering RNA (siRNA)-mediated downregulation of Gasdermin E (GSDME) inhibited pyroptosis, suggesting that GSDME plays an essential role in this process. The upstream signaling pathway was further investigated through caspase-3 inhibition and caspase-8 knockdown, which demonstrated that pyroptosis induced by paclitaxel and nocodazole was mediated by the caspase-8/caspase-3/GSDME pathway. Moreover, during mitotic arrest, phosphorylation of IRF3, mediated by cGAS/TBK1, led to the formation of the RIPK1/FADD/caspase-8 complex, which subsequently activated caspase-8 and initiated downstream GSDME-mediated pyroptosis. Knockdown of components of this complex or mutation of the IRF3 phosphorylation site inhibited pyroptosis. Furthermore, in vivo experiments also demonstrated that paclitaxel inhibited tumor growth by inducing GSDME-mediated pyroptosis and activating the anti-tumor immune infiltration. TCGA data further suggested that ovarian cancer cases treated with paclitaxel, showing high expression of GSDME and caspase-3, exhibited a more favorable tumor immune microenvironment. This study not only elucidated the specific mechanism of pyroptosis mediated by phosphorylated IRF3 during prolonged mitotic arrest but also revealed that mitotic arrest-induced pyroptosis could enhance immune infiltration in ovarian cancer, providing valuable insights for clinical treatment strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"306"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546196","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":"Senescence-associated alterations in histone H3 modifications, HP1 alpha levels and distribution, and in the transcriptome of vascular smooth muscle cells in different types of senescence.","authors":"Agnieszka Gadecka, Marta Koblowska, Helena Kossowska, Roksana Iwanicka-Nowicka, Dorota Janiszewska, Grażyna Mosieniak, Krzysztof Bojakowski, Krzysztof Goryca, Anna Bielak-Zmijewska","doi":"10.1186/s12964-025-02315-8","DOIUrl":"10.1186/s12964-025-02315-8","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence is a fundamental process leading to organismal aging and age-related diseases. Alterations accompanying cellular senescence concern, among others, nucleus architecture, chromatin structure, DNA damage and gene expression. Some changes are universal for all types of senescence, but some characteristics are typical for a given senescence inductor or cell type. The aim of the study was to analyze senescence-associated alterations in chromatin modifications and look for differences depending on senescence type (replicative, RS and stress-induced premature senescence, SIPS) in vascular smooth muscle cells (VSMCs) in vitro. The alterations were compared with those observed in VSMCs derived from atherosclerotic plaques (ex vivo) and, to assess their universality, with those in senescent fibroblasts.</p><p><strong>Methods: </strong>We investigated the level and distribution of HP1α and H3 modifications that are markers of hetero- and euchromatin (H3K9me3, H3K27me3, H3K4me3, H3K9Ac - WB and IF), alterations in the transcriptomic profile (DNA microarray, qPCR), H3K4me3, H3K9me3 and HP1α protein distribution in the genome (ChIP-seq), and expression of enzymes involved in histone post-translational modifications (DNA microarray, qPCR, WB, IF).</p><p><strong>Results: </strong>Our results have shown that the decline in H3K4me3 and H3K9me3 modifications and in HP1α is a universal hallmark of senescence in all tested cell and senescence types, although the extent of the change depends on the senescence inductor. The distribution of H3K4me3 and H3K9me3 in the genome of VSMCs depends on the senescence type, and the transcriptomic analysis identified genes and processes specific to each type.</p><p><strong>Conclusions: </strong>We characterized senescence and cell type-dependent changes in chromatin-associated proteins and enzymes involved in histone H3 decoration which, in consequence, impact senescence-associated gene expression. We can conclude that certain similar alterations occur in senescent VSMCs ex vivo, although inter-individual differences usually obscure them. Our results clearly showed that differences existed not only between young and senescent cells but also between SIPS and RS ones. The subtle differences between various SIPS types suggest that various stressors activate the same cellular mechanisms. This study can serve as a starting point to search for factors that may be used to distinguish between SIPS and RS, which in turn could be helpful in defining conditions responsible for accelerated aging.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"321"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546200","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":"IL-23 promotes neuronal ferroptosis via IL-23R/STAT3 signaling after traumatic brain injury.","authors":"Bo Chen, Guihong Shi, Jianye Xu, Xu Zhang, Yanlin Zhu, Lei Li, Cong Wang, Dilmurat Gheyret, Jinchao Wang, Xilei Liu, Yiyao Cao, Rui Tan, Yuan Zhou, RongCai Jiang, Shenghui Li, Tuo Li, Xiao Liu, Xin Chen, Guili Yang, Jianning Zhang, Shu Zhang","doi":"10.1186/s12964-025-02319-4","DOIUrl":"10.1186/s12964-025-02319-4","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) causes significant neuronal death, but the underlying mechanisms remain poorly understood. The role of interleukin-23 (IL-23) signaling in post-traumatic neuronal injury requires investigation.</p><p><strong>Methods: </strong>We examined IL-23 levels in clinical samples from TBI patients and healthy controls. Using a mouse TBI model, we investigated the effects of IL-23 neutralization and explored the cellular mechanisms through analysis of IL-23 receptor expression, JAK2/STAT3 pathway activation, and macrophage infiltration.</p><p><strong>Results: </strong>We found elevated IL-23 levels in both serum and brain tissues of TBI patients. TBI induced neuronal IL-23 receptor expression and activated the JAK2/STAT3 pathway. Infiltrating macrophages were identified as the main IL-23 source, recruited by neuron-derived C-C motif chemokine ligand 2 (CCL2). IL-23 neutralization or CCL2 blockade reduced neuronal ferroptosis and improved neurological outcomes in the mouse model.</p><p><strong>Conclusions: </strong>Our findings reveal a novel CCL2-macrophage-IL-23 axis in TBI pathogenesis, where IL-23 promotes neuronal ferroptosis through direct receptor-mediated effects. Targeting this pathway represents a potential therapeutic strategy for TBI treatment.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"317"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546192","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":"IGF2BP3 promotes autophagy-mediated TNBC metastasis via m6A-dependent, cap-independent c-Met translation.","authors":"Zi-Wen Wang, Yi-Han Li, Meng-Yuan Cai, Xu Zhang, Ruo-Xi Xu, Hai-Yan Yang, Yu-Zhou Huang, Liang Shi, Ji-Fu Wei, Qiang Ding","doi":"10.1186/s12964-025-02316-7","DOIUrl":"10.1186/s12964-025-02316-7","url":null,"abstract":"<p><strong>Background: </strong>Metastatic tumors pose clinical treatment challenges due to their high adaptability to diverse environments. The cooperation of epigenetic modifications and metabolic adaptations enables tumor cells to dynamically adjust for survival in variable environments, which is crucial for tumor metastasis and worth exploring in depth.</p><p><strong>Methods: </strong>RNA immunoprecipitation sequencing, transmission electron microscopy photograph and GFP-mCherry-LC3 fluorescence imaging were employed to reveal the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in triple-negative breast cancer (TNBC) cells. Then, in the presence of rapamycin, further experiments showed that IGF2BP3's role in TNBC metastasis was autophagy-mediated. Methylated RNA immunoprecipitation sequencing, luciferase assays and co-immunoprecipitation mass spectrometry showed that IGF2BP3 promoted mRNA translation initiation in an N6-methyladenosine (m6A)-dependent manner.</p><p><strong>Results: </strong>We found that IGF2BP3 could link epigenetic modification and metabolic adaptation to promote autophagy-mediated TNBC metastasis. As an m6A binding protein that is specifically highly expressed in TNBC, IGF2BP3 could bind to the m6A motif of c-Met mRNA, regulating autophagy-mediated epithelial-to-mesenchymal transition via the c-Met/PI3K/AKT/mTOR pathway. Moreover, IGF2BP3 recruited eIF4G2 as a collaborator, promoting c-Met protein expression by facilitating m6A-dependent and cap-independent mRNA translation initiation, rather than affecting mRNA stability.</p><p><strong>Conclusions: </strong>Our study expands the understanding of IGF2BP3's role in TNBC metastasis by establishing its function in regulating autophagy. Notably, IGF2BP3 could bind to the m6A motif on the 5' and 3' untranslated regions (UTRs) of c-Met mRNA to facilitate its translation in a cap-independent manner.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"303"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546191","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":"Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.","authors":"Mincong Shu, Yuhan Liu, Jianbin Wang","doi":"10.1186/s12964-025-02327-4","DOIUrl":"10.1186/s12964-025-02327-4","url":null,"abstract":"<p><p>Serine is a non-essential amino acid, serving as a precursor for other amino acids, lipids, and nucleotide synthesis. Its supply is ensured by two main mechanisms: exogenous uptake and endogenous synthesis. The serine synthesis pathway (SSP) connects glycolysis with the one-carbon cycle and plays an important role in cellular homeostasis by regulating substance synthesis, redox homeostasis, and gene expression. The de novo SSP involves three successive enzymatic reactions catalyzed by phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). Post-translational modifications (PTMs), as essential regulatory mechanisms of proteins, play pivotal roles in physiological and pathological processes. This review focuses on the regulatory mode of PTMs on PHGDH, PSAT1, and PSPH, including phosphorylation, ubiquitination, acetylation, methylation, S-palmitoylation, S-nitrosylation, deamidation, SUMOylation, and lactylation. We summarize how these PTMs participate in the metabolic reprogramming of SSP. It helps us better understand the molecular mechanisms and physiological significance of the PTM network in serine synthetic metabolism, providing guidance for subsequent research and development in the future.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"311"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546198","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":"Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.","authors":"Yiyi Shou, Ruiqi Liu, Hao Xiong, Keke Xu, Xiaoyan Chen, Luanluan Huang, Yitian Zhang, Hailong Sheng, Haibo Zhang, Yanwei Lu","doi":"10.1186/s12964-025-02328-3","DOIUrl":"10.1186/s12964-025-02328-3","url":null,"abstract":"<p><p>Cancer cells experience metabolic reprogramming to enhance the synthesis of nitrogen and carbon, facilitating the production of macromolecules essential for tumor proliferation and growth. A central strategy in this process involves reducing catabolic activities and managing nitrogen, thereby improving the efficiency of nitrogen utilization. The urea cycle (UC), conventionally recognized for its role in detoxifying excess nitrogen in the liver, is pivotal in this metabolic transition. Beyond the hepatic environment, the differential expression of UC enzymes facilitates the utilization of nitrogen for the synthesis of metabolic intermediates, thereby addressing the cellular metabolic requirements, especially under conditions of nutrient scarcity. In oncogenic contexts, the expression and regulation of UC enzymes undergo substantial modification, promoting metabolic reprogramming to optimize nitrogen assimilation into cellular biomass. This reconfigured UC not only enhances tumor cell survival but also plays a pivotal role in the reorganization of the tumor microenvironment (TME), thereby aiding in immune evasion. This review examines the mechanistic underpinnings of urea cycle dysregulation (UCD) in cancer, highlighting its dynamic roles across various tumor types and stages, as well as the therapeutic implications of these alterations. Understanding how UC relaxation promotes metabolic flexibility and immune evasion may help develop novel therapeutic strategies that target tumor metabolism and enhance anti-cancer immunity.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"307"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546244","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":"Mechanisms of electroacupuncture-induced neuroprotection in acute stroke rats: the role of astrocyte-mediated mitochondrial transfer.","authors":"Yang Guo, Tiancong Fu, Yupei Cheng, Yuxuan Li, Runchen Zhang, Qingtao Ma, Guanran Wang, Wenhua Ning, Wen Fan, Juntao Yang, Mengxiong Zhao, Bohan Liu, Can Wang, Liang Gao, Zhifang Xu, Yi Guo, Xiaoyu Dai, Jiangwei Shi","doi":"10.1186/s12964-025-02287-9","DOIUrl":"10.1186/s12964-025-02287-9","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke significantly threatens human health, and current treatments remain limited, necessitating novel strategies. Mitochondrial transfer between neurons represents a crucial endogenous neuroprotective mechanism.</p><p><strong>Objective: </strong>This study investigated whether electroacupuncture enhances mitochondrial transfer from astrocytes to damaged neurons during acute cerebral ischemia, promoting neuroprotection.</p><p><strong>Methods: </strong>A middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro were employed. Neurobehavioral assessments, electron microscopy, multiplex immunofluorescence, tissue quantification, western blotting, qRT-PCR, transcriptomics, and proteomics were conducted to evaluate mitochondrial distribution, function, and intercellular transfer under electroacupuncture preconditioning and intervention.</p><p><strong>Results: </strong>Electroacupuncture significantly improved neurological outcomes and reduced brain tissue damage in MCAO rats. It facilitated mitochondrial transfer from astrocytes to neurons, increased functional mitochondria within neurons, and reduced neuronal apoptosis. These effects may involve regulation of the CD38-cADPR-Ca2 + signaling pathway and proteins associated with tunneling nanotubes (TNTs), such as F-actin, Miro1, TRAK1, and KIF5b.</p><p><strong>Conclusion: </strong>Electroacupuncture enhances mitochondrial transfer and function, exerting neuroprotective effects during acute ischemic stroke. This study highlights the potential of electroacupuncture as a therapeutic approach and identifies novel targets for brain protection strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"316"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546194","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":"ACPA-Induced ATP release and K⁺ efflux trigger NLRP3 inflammasome activation in rheumatoid arthritis.","authors":"Li Cai, Kai Zhang, Jian Gao, Bing Xiao, Meng Li, Xiangyun Meng, Zhipeng Chen, Xiaoling Chen, Shixian Chen, Juan Li","doi":"10.1186/s12964-025-02331-8","DOIUrl":"10.1186/s12964-025-02331-8","url":null,"abstract":"<p><strong>Objectives: </strong>Anti-citrullinated protein antibodies (ACPA) is one of the key inducers of the initiation and maintenance of the immune-inflammatory response in Rheumatoid arthritis (RA), yet evidence is lacking on how ACPA drives the inflammatory response.</p><p><strong>Methods: </strong>Citrullinated collagen-induced arthritis (C-CIA) were performed to evaluate the inflammatory response, especially NLRP3 inflammasome activation, in ACPA + arthritis model. Macrophages differentiated from THP-1 cell line were stimulated by ACPA purified from RA patients' serum, and the localization and interaction of molecules involved in NLRP3 inflammasome were analyzed by confocal microscopy and immunoprecipitation.</p><p><strong>Results: </strong>Mice with arthritis induced by citrullinated collagen showed higher levels of ACPA and enhanced activation of the NLRP3 inflammasome. This was evidenced by increased levels of IL-1β in the peripheral blood and more pronounced pyroptosis and caspase-1 (p20) expression in the synovial tissue, compared to mice induced with common collagen. ACPA induced overactivation of NLRP3 inflammasome in THP-1-differentiated macrophages in vitro. ACPA recruits SFK kinase by binding to integrin α₅β₁, induces C-terminal phosphorylation of Panx-1, and opens pannexin channel to release ATP; In addition, ACPA mediates the outflow of K⁺ into the extracellular by activating TWIK2 channel. These two signaling axes collectively lead to the activation of the NLRP3 inflammasome.</p><p><strong>Conclusion: </strong>Our study demonstrates that ACPA can trigger both the priming and activation of the NLRP3 inflammasome. This process involves the release of ATP and the efflux of K⁺.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"302"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546186","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":"Gremlin1 repression-mediated mitochondrial network hyperfunction contributes to TCE-induced zebrafish cardiac defects.","authors":"Huifang Deng, Zhijie Bai, Chaoji Huangfu, Ningning Wang, Miao Chen, Gaofu Li, Congshu Huang, Ting Ao, Xiang Tang, Tiantian Xia, Li Zhang, Pan Shen, Wei Zhou, Yue Gao","doi":"10.1186/s12964-025-02314-9","DOIUrl":"10.1186/s12964-025-02314-9","url":null,"abstract":"<p><strong>Background: </strong>Trichloroethylene (TCE) is a ubiquitous pollutant with potential capacity to induce congenital heart disease (CHD). However, the mechanisms underlying TCE-induced CHD are largely unraveled.</p><p><strong>Methods: </strong>We exposed zebrafish embryos to TCE to investigate its cardiac development toxicity and related response factor through bulk RNA sequencing. We constructed transgenic fluorescent fish and employed the CRISPR/dCas9 system along with single-cell RNA sequencing to identify the genetic cause of TCE-induced CHD.</p><p><strong>Results: </strong>We found that early-stage exposure to TCE induced significant cardiac defects characterized by elongated SV-BA distance, thinned myocardium, and attenuated contractility. Gremlin1 encoding gene, grem1a, a putative target showing high expression at the beginning of cardiac development, was sharply down-regulated by TCE. Consistently, grem1a knockdown in zebrafish induced cardiac phenotypes generally like those of the TCE-treated group, accompanying the disarrangement of myofibril structure. Single-cell RNA-seq depicted that mitochondrial respiration in grem1a-repressed cardiomyocytes was greatly enhanced, ultimately leading to a branch from the normal trajectory of myocardial development. Accordingly, in vitro results demonstrated that GREM1 repression increased mitochondrial content, ATP production, mitochondrial reactive oxygen species, mitochondrial membrane potential, and disrupted myofibril expansion in hPSC-CMs.</p><p><strong>Conclusions: </strong>These results suggested that TCE-induced gremlin1 repression could result in mitochondrial hyperfunction, thereby hampering cardiomyocyte development and causing cardiac defects in zebrafish embryos. This study not only provided a novel insight into the etiology for environmental stressor-caused cardiac development defects, but also offered a potential therapeutic and preventive target for TCE-induced CHD.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"318"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546189","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":"Hormonally upregulated neu tumor-associated kinase (HUNK) modulates gastric cancer progression through the regulation of cell homeostasis.","authors":"Giuseppina di Paola, Francesco Albano, Pietro Zoppoli, Daniele Bravoco, Teresa D'Amore, Elena Amendola, Valeria Lucci, Luca Roberto, Mariarita Brancaccio, Paolo Salerno, Giovanni Calice, Simona Laurino, Sabino Russi, Cristofaro De Stefano, Monica Maiello, Giuseppe Merla, Geppino Falco, Pellegrino Mazzone","doi":"10.1186/s12964-025-02329-2","DOIUrl":"10.1186/s12964-025-02329-2","url":null,"abstract":"<p><p>Gastric cancer (GC) is a neoplasia with an increase in incidence and mortality over the next years. Currently, the treatment of this malignancy consists of surgery in association with the administration of platinum compounds or 5-FU capecitabine. The identification of novel biomarkers related to the GC progression is a key point in re-modulating the pharmacological treatment to get a more efficient patient response. In this study, we reported that Hormonally Upregulated Neu tumor-associated Kinase (HUNK) promotes gastric cancer progression by regulating cell homeostasis. Particularly, we demonstrated that HUNK is responsible for the increase in gastric cancer cell proliferation through the binding and phosphorylation of p38 MAP kinase and that its depletion is associated with a reduction of survival both in gastric cancer cells and patient-derived organoids. Further, we reported that HUNK regulates positively the expression of MUC16/CA-125, a well-known cancer prognostic marker. Our findings shed light, for the first time, on the molecular mechanisms regulated by HUNK in gastric cancer cells making this kinase a promising candidate for novel targeted therapeutic strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"320"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546190","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}