Cell Communication and Signaling最新文献

{"title":"Multi-omics analysis reveals CMTR1 upregulation in cancer and roles in ribosomal protein gene expression and tumor growth.","authors":"Ion John Campeanu, Yuanyuan Jiang, Hilda Afisllari, Sijana Dzinic, Lisa Polin, Zeng-Quan Yang","doi":"10.1186/s12964-025-02147-6","DOIUrl":"https://doi.org/10.1186/s12964-025-02147-6","url":null,"abstract":"<p><strong>Background: </strong>CMTR1 (cap methyltransferase 1), a key nuclear mRNA cap methyltransferase, catalyzes 2'-O-methylation of the first transcribed nucleotide, a critical step in mRNA cap formation. Previous studies have implicated CMTR1 in embryonic stem cell differentiation and immune responses during viral infection; however, its role in cancer biology remains largely unexplored. This study aims to elucidate CMTR1's function in cancer progression and evaluate its potential as a novel therapeutic target in certain cancer types.</p><p><strong>Methods: </strong>We conducted a comprehensive multi-omics analysis of CMTR1 across various human cancers using TCGA and CPTAC datasets. Functional studies were performed using CRISPR-mediated knockout and siRNA knockdown in human and mouse basal-like breast cancer models. Transcriptomic and pathway enrichment analyses were carried out in CMTR1 knockout/knockdown models to identify CMTR1-regulated genes. In silico screening and biochemical assays were employed to identify novel CMTR1 inhibitors.</p><p><strong>Results: </strong>Multi-omics analysis revealed that CMTR1 is significantly upregulated at the mRNA, protein, and phosphoprotein levels across multiple cancer types in the TCGA and CPTAC datasets. Functional studies demonstrated that CMTR1 depletion significantly inhibits tumor growth both in vitro and in vivo. Transcriptomic analysis of CMTR1 knockout cells revealed that CMTR1 primarily regulates ribosomal protein genes and other transcripts containing 5' Terminal Oligopyrimidine (TOP) motifs. Additionally, CMTR1 affects the expression of snoRNA host genes and snoRNAs, suggesting a broader role in RNA metabolism. Mechanistic studies indicated that CMTR1's target specificity is partly determined by mRNA structure, particularly the presence of 5'TOP motifs. Finally, through in silico screening and biochemical assays, we identified several novel CMTR1 inhibitors, including N97911, which demonstrated in vitro growth inhibition activity in breast cancer cells.</p><p><strong>Conclusions: </strong>Our findings establish CMTR1 as an important player in cancer biology, regulating critical aspects of RNA metabolism and ribosome biogenesis. The study highlights CMTR1's potential as a therapeutic target in certain cancer types and provides a foundation for developing novel cancer treatments targeting mRNA cap methylation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"197"},"PeriodicalIF":8.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993002","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":"CTSL-2 upon specifically recognizing Vibrio splendidus directly cleaves complement C3 to promote the bacterial phagocytosis and degradation in oyster.","authors":"Qiuyan Guo, Wenwen Yang, Weishuai Shan, Hongsheng Yao, Xiangqi Shi, Lingling Wang, Jiejie Sun, Linsheng Song","doi":"10.1186/s12964-025-02205-z","DOIUrl":"https://doi.org/10.1186/s12964-025-02205-z","url":null,"abstract":"<p><p>Cathepsin L (CTSL) as a cysteine cathepsin protease mediates complement C3 cleavage and pathogen degradation. In the present study, a CTSL homolog was identified from Crassostrea gigas (designated as CgCTSL-2). Its mRNA expression increased significantly in hemocytes after Vibrio splendidus stimulation. The activity of rCgCTSL-2 was induced after incubation with LPS or V. splendidus in Ca²⁺-dependent manner. rCgCTSL-2 could specifically bound V. splendidus in Ca²⁺-dependent manner. The co-localization of rCgCTSL-2 and V. splendidus was observed in cell-free hemolymph. Upon binding V. splendidus, CgCTSL-2 interacted with CgC3 in cell-free hemolymph and hemocytes. CgC3 fragments in CgCTSL-2-RNAi oysters and full length CgC3 in rCgCTSL-2-treated oysters were both reduced in cell-free hemolymph, respectively. CgC3 fragments were accumulated in CgCTSL-2-RNAi or rCgCTSL-2-treated oysters. The co-localizations of V. splendidus, CgC3, CgCD18, CgCTSL-2 and lysosomes were observed in hemocytes. These results suggested that CgCTSL-2 upon binding V. splendidus directly interacted with CgC3 to lead to CgC3 cleavage and then CgC3 fragments coated on V. splendidus were mediated by CgCD18 into CTSL-2-lysosome pathway.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"198"},"PeriodicalIF":8.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056236","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":"CDO1 phosphorylation is required for IL-6-induced tumor cell proliferation through governing cysteine availability.","authors":"Xin Li, Zhe Zhao, Hongping Ye, Dan Li, Xiaoke Huang, Jong-Ho Lee, Rui Liu","doi":"10.1186/s12964-025-02189-w","DOIUrl":"https://doi.org/10.1186/s12964-025-02189-w","url":null,"abstract":"<p><p>Inflammatory pathways are often hijacked by cancer cells to favor their own proliferation and survival. Cysteine dioxygenase type 1 (CDO1), an iron-dependent thiol dioxygenase enzyme, catalyzes the rate-limiting step for cysteine oxidation, and so that functions as an important regulator of cellular cysteine availability. However, whether inflammatory environment affects CDO1 activity and cysteine oxidation and its potential impact on tumor growth remains substantially elusive. In the present study, we demonstrate that CDO1 activity and cysteine oxidation is inhibited upon IL-6 treatment, without noticeable alterations in CDO1 expression. Mechanistically, AKT1 phosphorylates CDO1 T89 under IL-6 treatment, which represses CDO1 enzymatic activity by disrupting iron incorporation. Further, AKT1-mediated CDO1 T89 phosphorylation is required for IL-6-elicited oral squamous cell carcinoma (OSCC) growth, and is associated with the progression of OSCC development. The present data discover a new mechanism by which AKT1-mediated CDO1 T89 phosphorylation governs cysteine oxidation to support OSCC growth, thereby highlighting its value as a potential anti-tumor target.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"194"},"PeriodicalIF":8.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035976","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":"Probiotics promote cellular wound healing responses by modulating the PI3K and TGF-β/Smad signaling pathways.","authors":"Sixuan Zhang, Yvonne Elbs-Glatz, Siyuan Tao, Steven Schmitt, Zhihao Li, Markus Rottmar, Katharina Maniura-Weber, Qun Ren","doi":"10.1186/s12964-025-02179-y","DOIUrl":"https://doi.org/10.1186/s12964-025-02179-y","url":null,"abstract":"<p><strong>Background: </strong>Skin wound healing represents a dynamic and intricate biological process involving the coordinated efforts of various cellular and molecular components to restore tissue integrity and functionality. Among the myriads of cellular events orchestrating wound closure, fibroblast migration and the regulation of fibrosis play pivotal roles in determining the outcome of wound healing. In recent years, probiotic therapy has emerged as a promising strategy for modulating wound healing and fibrosis. Here, we aim to investigate the effect of bacterial probiotics on cell migration and anti-fibrotic response of human dermal fibroblast (HDFs).</p><p><strong>Methods: </strong>Probiotic mixture BioK was co-cultured with HDFs in vitro to assess its impact on fibroblast migration, gene expression, and protein production associated with important processes in wound healing. Gene expression was investigated by transcriptomic analysis and confirmed by RT-qPCR. Protein levels of the identified genes were evaluated by ELISA. The role of lactic acid, produced by BioK, in mediating pH-related effects on fibroblast activity was further examined.</p><p><strong>Results: </strong>We observed that BioK effectively promoted HDFs migration in vitro, which was found to be related to the up-regulation of genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathways such as Paxillin, PI3K, PKC and ITG-β1. Interestingly, we also found that BioK down-regulated the expression of Nox-4, α-SMA and Col-I in TGF-Smad signaling pathways, which are involved in the differentiation of fibroblasts to myofibroblasts, and extracellular matrix type I collagen production, demonstrating its potential in reducing formation of fibrosis and scars. One of the acting factors for such down-regulation was identified to be BioK-produced lactic acid, which is known to lower the surrounding pH and to play a major role in fibroblast activity and wound healing.</p><p><strong>Conclusions: </strong>This study demonstrates BioK's beneficial effects on fibroblast migration and its potential to mitigate fibrosis through pH modulation and pathway-specific gene regulation. These findings enhance our understanding of probiotic action on wound healing and offer promising therapeutic insights for the reduction of scar formation.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"195"},"PeriodicalIF":8.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040867","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":"Glucose- and glutamine-driven de novo nucleotide synthesis facilitates WSSV replication in shrimp.","authors":"Cong-Yan Chen, Chih-Ling Chen, Yen Siong Ng, Der-Yen Lee, Shih-Shun Lin, Chien-Kang Huang, Ramya Kumar, Han-Ching Wang","doi":"10.1186/s12964-025-02186-z","DOIUrl":"https://doi.org/10.1186/s12964-025-02186-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Viruses rely on host metabolism to complete their replication cycle. White spot syndrome virus (WSSV), a major pathogen in shrimp aquaculture, hijacks host metabolic pathways to fulfill its biosynthetic and energetic needs. Previous studies have demonstrated that WSSV promotes aerobic glycolysis (Warburg effect) and glutaminolysis during its replication stage (12 hpi). Therefore, glucose and glutamine serve as crucial metabolites for viral replication. Additionally, de novo nucleotide synthesis, including the pentose phosphate pathway and purine/pyrimidine synthesis, is significantly activated during WSSV infection. However, the precise association between WSSV and host glucose and glutamine metabolism in driving de novo nucleotide synthesis remains unclear. This study aimed to investigate the involvement of glucose and glutamine in nucleotide metabolism during WSSV replication and to elucidate how WSSV reprograms these pathways to facilitate its pathogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To assess changes in metabolic flux during WSSV replication, LC-ESI-MS-based isotopically labeled glucose ([U-&lt;sup&gt;13&lt;/sup&gt;C] glucose) and glutamine ([A-&lt;sup&gt;15&lt;/sup&gt;N] glutamine) were used as metabolic tracers in in vivo experiments with white shrimp (Litopenaeus vannamei). The in vivo experiments were also conducted to measure the expression and enzymatic activity of genes involved in nucleotide metabolism. Additionally, in vivo dsRNA-mediated gene silencing was employed to evaluate the roles of these genes in WSSV replication. Pharmacological inhibitors targeting the Ras-PI3K-Akt-mTOR pathway were also applied to investigate its regulatory role in WSSV-induced nucleotide metabolic reprogramming.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The metabolite tracking analysis confirmed that de novo nucleotide synthesis was significantly activated at the WSSV replication stage (12 hpi). Glucose metabolism is preferentially reprogrammed to support purine synthesis, while glutamine uptake is significantly increased and contributes to both purine and pyrimidine synthesis. Consistently, gene expression and enzymatic activity analyses, along with gene silencing experiments, indicated the critical role of de novo nucleotide synthesis in supporting viral replication. However, while the inhibition of the Ras-PI3K-Akt-mTOR pathway suggested its involvement in regulating nucleotide metabolism, no consistent effect on WSSV replication was observed, suggesting the presence of alternative regulatory mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study demonstrates that WSSV infection induces specific metabolic reprogramming of glucose and glutamine utilization to facilitate de novo nucleotide synthesis in shrimp. These metabolic changes provide the necessary precursors for nucleotide synthesis, supporting WSSV replication and pathogenesis. The findings offer novel insights into the metabolic strategies employed by WSSV and suggest potential targets f","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"191"},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042543","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":"Mechanical cues rewire lipid metabolism and support chemoresistance in epithelial ovarian cancer cell lines OVCAR3 and SKOV3.","authors":"Martina Karasová, Maximilian Jobst, Denise Framke, Janice Bergen, Samuel Meier-Menches, Bernhard Keppler, Gunda Koellensperger, Jürgen Zanghellini, Christopher Gerner, Giorgia Del Favero","doi":"10.1186/s12964-025-02144-9","DOIUrl":"https://doi.org/10.1186/s12964-025-02144-9","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC) is one of the deadliest cancers in women, and acquired chemoresistance is a major contributor of aggressive phenotypes. Overcoming treatment failure and disease recurrence is therefore an ambitious goal. Ovarian cancer develops in a biophysically challenging environment where the cells are constantly exposed to mechanical deformation originating in the abdomen and shear stress caused by the accumulation of ascitic fluid in the peritoneal cavity. Therefore, mechanical stimulation can be seen as an inseparable part of the tumor microenvironment. The role of biomechanics in shaping tumor metabolism is emerging and promises to be a real game changer in the field of cancer biology. Focusing on two different epithelial ovarian cancer cell lines (SKOV3 and OVCAR3), we explored the impact of shear stress on cellular behavior driven by mechanosensitive transcription factors (TFs). Here, we report data linking physical triggers to the alteration of lipid metabolism, ultimately supporting increased chemoresistance. Mechanistically, shear stress induced adaptation of cell membrane and actin cytoskeleton which were accompanied by the regulation of nuclear translocation of SREBP2 and YAP1. This was associated with increased cholesterol uptake/biosynthesis and decreased sensitivity to the ruthenium-based anticancer drug BOLD-100. Overall, the present study contributes to shedding light on the molecular pathways connecting mechanical cues, tumor metabolism and drug responsiveness.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"193"},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059177","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":"Mitochondrial DNA signals driving immune responses: Why, How, Where?","authors":"Luca Giordano, Sarah A Ware, Claudia J Lagranha, Brett A Kaufman","doi":"10.1186/s12964-025-02042-0","DOIUrl":"https://doi.org/10.1186/s12964-025-02042-0","url":null,"abstract":"<p><p>There has been a recent expansion in our understanding of DNA-sensing mechanisms. Mitochondrial dysfunction, oxidative and proteostatic stresses, instability and impaired disposal of nucleoids cause the release of mitochondrial DNA (mtDNA) from the mitochondria in several human diseases, as well as in cell culture and animal models. Mitochondrial DNA mislocalized to the cytosol and/or the extracellular compartments can trigger innate immune and inflammation responses by binding DNA-sensing receptors (DSRs). Here, we define the features that make mtDNA highly immunogenic and the mechanisms of its release from the mitochondria into the cytosol and the extracellular compartments. We describe the major DSRs that bind mtDNA such as cyclic guanosine-monophosphate-adenosine-monophosphate synthase (cGAS), Z-DNA-binding protein 1 (ZBP1), NOD-, LRR-, and PYD- domain-containing protein 3 receptor (NLRP3), absent in melanoma 2 (AIM2) and toll-like receptor 9 (TLR9), and their downstream signaling cascades. We summarize the key findings, novelties, and gaps of mislocalized mtDNA as a driving signal of immune responses in vascular, metabolic, kidney, lung, and neurodegenerative diseases, as well as viral and bacterial infections. Finally, we define common strategies to induce or inhibit mtDNA release and propose challenges to advance the field.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"192"},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058319","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":"Phospho-regulated tethering of focal adhesion kinase to vinculin links force transduction to focal adhesion signaling.","authors":"Karen Diaz-Palacios, Pilar López Navajas, Bárbara Rodrigo Martín, Ruth Matesanz, Juan R Luque-Ortega, Asier Echarri, Daniel Lietha","doi":"10.1186/s12964-025-02201-3","DOIUrl":"https://doi.org/10.1186/s12964-025-02201-3","url":null,"abstract":"<p><p>Focal Adhesion Kinase (FAK) is a key signaling molecule in focal adhesions (FAs) orchestrating the formation, maturation and turnover of the FA complex. A controlled FA lifecycle is essential for various cellular processes requiring mesenchymal cell migration and is harnessed by advanced cancers to initiate cancer invasion and metastasis. The mechanical force for migration is transmitted from actin stress fibers to FAs via specialized force transduction components in FAs. These forces are known to activate FA signaling, suggesting a communication between FA force transduction and FA signaling components, yet how this occurs mechanistically is unknown. Here we demonstrate that paxillin can act as an adaptor protein to connect FAK with the force transduction component vinculin. Our data show that this connection forms inefficient in the basal state but suggest Y925 phosphorylation in FAK as a key mechanism for optimal formation of the FAK:paxillin:vinculin linkage. This is achieved by switching binding of the paxillin LD2 motif from FAK to vinculin while keeping paxillin LD4 tethered to FAK. We further provide the first high-resolution crystal structure of LD2 bound to the vinculin tail domain, which importantly shows that vinculin can simultaneously link to actin. This therefore ensures an intact force transduction role of vinculin while tethered via paxillin to the signaling apparatus in FAs. With this data, all interactions of the force transmitting tether to FAK are structurally defined and we provide an atomic model for FAK force activation. In summary, we propose a phospho-regulated connection between signaling and force transduction components in FAs allowing for force induced activation of FA signaling.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"190"},"PeriodicalIF":8.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063255","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":"Mannose and PMI depletion overcomes radiation resistance in HPV-negative head and neck cancer.","authors":"Tongchuan Wang, Connor Brown, Niamh Doherty, Niall M Byrne, Rayhanul Islam, Meabh Doherty, Jie Feng, Cancan Yin, Sarah Chambers, Lydia McQuoid, Letitia Mohamed-Smith, Karl T Butterworth, Emma M Kerr, Jonathan A Coulter","doi":"10.1186/s12964-025-02204-0","DOIUrl":"https://doi.org/10.1186/s12964-025-02204-0","url":null,"abstract":"<p><p>Radiotherapy is critical component of multidisciplinary cancer care, used as a primary and adjuvant treatment for patients with head and neck squamous cell carcinoma. This study investigates how mannose, a naturally occurring monosaccharide, combined with phosphomannose isomerase (PMI) depletion, enhances the sensitivity of HPV-negative head and neck tumour models to radiation. Isogenic PMI knockout models were generated by CRISPR/Cas9 gene editing, yielding a 20-fold increase in sensitivity to mannose in vitro, and causing significant tumour growth delay in vivo. This effect is driven by metabolic reprogramming, resulting in potent glycolytic suppression coupled with consistent depletion of ATP and glycolytic intermediates in PMI-depleted models. Functionally, these changes impede DNA damage repair following radiation, resulting in a significant increase in radiation sensitivity. Mannose and PMI ablation supressed both oxygen consumption rate and extracellular acidification, pushing cells towards a state of metabolic quiescence, effects contributing to increased radiation sensitivity under both normoxic and hypoxic conditions. In 3D-tumoursphere models, metabolic suppression by mannose and PMI depletion was shown to elevate intra-tumoursphere oxygen levels, contributing to significant in vitro oxygen-mediated radiosensitisation. These findings position PMI as a promising anti-tumour target, highlighting the potential of mannose as a metabolic radiosensitiser enhancing cancer treatment efficacy.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"189"},"PeriodicalIF":8.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050985","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":"IGF-1 promotes trophectoderm cell proliferation of porcine embryos by activating the Wnt/β-catenin pathway.","authors":"Min Ju Kim, Hyo-Gu Kang, Se-Been Jeon, Ji Hyeon Yun, Eun Young Choi, Pil-Soo Jeong, Bong-Seok Song, Sun-Uk Kim, Seong-Keun Cho, Bo-Woong Sim","doi":"10.1186/s12964-025-02191-2","DOIUrl":"https://doi.org/10.1186/s12964-025-02191-2","url":null,"abstract":"<p><strong>Background: </strong>Insulin-like growth factor 1 (IGF-1) influences various aspects of embryogenesis, including embryonic development. This study investigated the effects of IGF-1 on early embryonic development in pig embryos, focusing on its interaction with the Wnt/β-catenin signaling pathway, a key regulator of cell adhesion and proliferation.</p><p><strong>Methods: </strong>Porcine embryos were used for experiments with chemical treatments to study blastocyst development and underlying mechanism. Apoptosis, immunochemistry, gene expression, and protein quantification were performed, with statistical significance assessed.</p><p><strong>Results: </strong>IGF-1 treatment during the early stages of embryonic development significantly enhanced developmental parameters, in particular blastocyst formation rates. Interestingly, IGF-1 increased trophectoderm (TE) cell proliferation. The TE is an essential component of the blastocyst, maintaining its structure. Successful development of pig embryos was dependent on the proper formation and function of the TE. IGF-1 upregulated the expression of functional proteins related to TE differentiation and tight junctions. Notably, these effects were more pronounced when IGF-1 treatment was performed during the last 3 days of embryonic development (days 3-6) compared to the first 3 days (days 0-3). In addition, we found that IGF-1 promoted activation of the Wnt/β-catenin signaling pathway, including increasing β-catenin levels and related gene expression. To confirm the interaction between IGF-1 signaling and the Wnt/β-catenin pathway in TE development, embryos were cultured with picropodophyllin, an IGF-1 receptor inhibitor. Picropodophyllin suppressed developmental parameters, β-catenin levels, TE cell differentiation, and tight junction formation. These effects were successfully rescued by IGF-1 and the Wnt/β-catenin signaling activator ChiR99021.</p><p><strong>Conclusion: </strong>Our findings provide new insights into the interaction between IGF-1 and the Wnt/β-catenin signaling pathway during embryogenesis and highlight the potential of IGF-1 to improve reproductive outcomes by enhancing TE formation and quality.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"188"},"PeriodicalIF":8.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058845","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}