International Journal of Biochemistry & Cell Biology最新文献

{"title":"Syndecan-2 positively regulates Wnt/β-catenin signaling in breast cancer cells","authors":"Leyli Naraghi ,&nbsp;Alexey Koval ,&nbsp;Vladimir L. Katanaev ,&nbsp;S.Mahmoud A Najafi","doi":"10.1016/j.biocel.2025.106853","DOIUrl":"10.1016/j.biocel.2025.106853","url":null,"abstract":"<div><div>Syndecans are a family of four-member transmembrane heparan sulfate proteoglycans that bind to various extracellular biomolecules, such as Wnt ligands, via their heparan sulfate chains, thereby controlling a variety of cellular processes. When dysregulated, syndecans can affect tumorigenesis and cancer progression by modulating key signaling pathways involved in the regulation of biological functions. Aberrant activation of Wnt/β-catenin signaling is a hallmark of many human tumors, including breast cancer. Studying the interplay between syndecans and Wnt signaling in human cancers is beneficial for identifying new therapeutic strategies, understanding tumor behavior and improving patient outcomes. Syndecan-2 is predominantly expressed by mesenchymal cells, and its overexpression in tumors of epithelial origin appears to induce aggressive behavior. Here, by measuring β-catenin cytoplasmic stabilization and transcriptional activity, we show that syndecan-2 expression significantly enhances the sensitivity of HEK293T cells and BT-20 triple-negative breast cancer cells to Wnt3a-induced activation of Wnt/β-catenin signaling. In addition, CRISPR/Cas9-mediated deletion of <em>SDC2</em>, the gene encoding syndecan-2, reduced β-catenin transcriptional activity in BT-20 cells in response to Wnt3a stimulation. This reduction was rescued by the re-expression of <em>SDC2</em>. Collectively, our results demonstrate that syndecan-2 is a positive regulator of canonical Wnt signaling. These results also suggest that syndecan-2 is a potential clinical target for inhibiting the progression of some human cancers.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"188 ","pages":"Article 106853"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-cancer effect of Loranthus micranthus via downregulation of inflammation, tryptophan catabolism and kynurenine synthesis","authors":"Azubuike P. Ebokaiwe ,&nbsp;Lingyu Li ,&nbsp;Ting Peng ,&nbsp;Emmanuel M. Njoya ,&nbsp;Zongyuan Zhou ,&nbsp;Euslar Nnenna Onu ,&nbsp;Guolin Zhang ,&nbsp;Wang Fei","doi":"10.1016/j.biocel.2025.106852","DOIUrl":"10.1016/j.biocel.2025.106852","url":null,"abstract":"<div><div>New therapeutic approaches are essential in the fight against breast cancer, which remains one of the top causes of mortality globally. Innovative and efficient methods of treating and preventing cancer has become expedient since its incidence rates are rising globally. Combining herbal extracts and chemotherapy have drawn a lot of attention in recent times as a cutting-edge cancer prevention approach. The wild parasitic plant <em>Loranthus micranthus</em> is extensively distributed throughout the world and is well-known for its therapeutic uses. Previous preclinical investigations indicated that the leaves and stem extracts of <em>L. micranthus</em> had the potential to suppress breast cancer. Investigating the anticancer effects of <em>L. micranthus</em> extracts through network pharmacology analysis, in vitro and in vivo experiments is the goal of the current study. Network pharmacology analysis revealed 207 targets and 30 bioactive phytoconstituents of <em>L. micranthus</em> associated with the metabolism of breast cancer. <em>L. micranthus</em> controlled the metabolism of tryptophan and nitrogen in breast cancer, according to KEGG analysis and in silico models. The results of the experiment showed that <em>L. micranthus</em> significantly reduced the synthesis of kynurenine in interferon-γ (IFN-γ)-stimulated breast cancer cells, downregulated important proteins involved in tryptophan catabolism, and produced no cytotoxic effects in human breast cancer cells (MCF 7 and MDA-MB 231) at the administered doses. The viability of T cells co-cultured with IFN-γ-treated breast cancer cells was also markedly enhanced by <em>L. micranthus</em> pre-treatment. The in vivo investigation showed a similar outcome, with <em>L. micranthus</em> treatment suppressing the inflammatory response, IDO activity/expression, lowering kynurenine levels, blocking CTLA-4 immune checkpoint and finally increasing the CD4⁺ T cell population in rats with DMBA-induced breast cancer.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"188 ","pages":"Article 106852"},"PeriodicalIF":2.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterozygous Kctd5 knockout mice exhibit abnormal lipid metabolism","authors":"Qiao Ling ,&nbsp;Manqi Cao ,&nbsp;Hua-an Zhang ,&nbsp;Xinjie Li ,&nbsp;Wenhao Wang ,&nbsp;Zhuohua Wang ,&nbsp;Qingrong Sun ,&nbsp;Zhijuan Liang ,&nbsp;Weiyi Huang ,&nbsp;Mengxuan Wang ,&nbsp;Xin Li ,&nbsp;Chuwen Lin ,&nbsp;Xuan Jiang ,&nbsp;Ji-An Pan ,&nbsp;Xiaoxue Peng","doi":"10.1016/j.biocel.2025.106851","DOIUrl":"10.1016/j.biocel.2025.106851","url":null,"abstract":"<div><div>The KCTD gene family is conserved across species, yet the knowledge of its function is limited. Recently, increasing studies focused on KCTD5 emerged. The functions of KCTD5 and its associations with various diseases were revealed. However, the function of KCTD5 <em>in vivo</em> has remained elusive. We generated <em>Kctd5</em>^+/- mice with the <em>Kctd5</em> gene’s exon 2 deleted using CRISPR/Cas9 technology. Breeding experiments on <em>Kctd5</em>^+/- mice showed that only <em>Kctd5</em>^+/- and <em>Kctd5</em>^+/+ mice could be born normally, while <em>Kctd5</em>^-/- embryos died in early embryonic development. Compared to <em>Kctd5</em>^+/+ mice, <em>Kctd5</em>^+/- mice have a shorter lifespan and exhibit spleen enlargement, abnormal blood cell counts, and metabolic disorders, including elevated cholesterol and triglyceride levels. Genome-wide gene expression analysis revealed that KCTD5 may affect the PPAR signaling pathway and subsequent the expression of Apo family genes, thereby regulating lipid metabolism. In summary, our study identified a previously unrecognized role of KCTD5 in regulating lipid metabolism and KCTD5 deficiency-induced animal phenotype, and revealed multiple correlations between KCTD5 and various molecules in mice.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"188 ","pages":"Article 106851"},"PeriodicalIF":2.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen-presenting cells orchestrate mixed inflammatory endotypes in atopic dermatitis","authors":"Shan Wang ,&nbsp;Jiahao Huang ,&nbsp;Fangping He ,&nbsp;Jiaxiao Lin,&nbsp;Xinyu Zheng,&nbsp;Na Zhang,&nbsp;Ailin Tao","doi":"10.1016/j.biocel.2025.106850","DOIUrl":"10.1016/j.biocel.2025.106850","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a complex pathogenesis involving aberrant activation of multiple immune responses. In recent years, targeted biologics have demonstrated significant efficacy in treating moderate to severe AD due to their precise mechanisms. However, the complex inflammatory profile of AD poses challenges for single-target biologics, leading to suboptimal therapeutic responses. By investigating the upstream induction mechanisms of mixed immune endotypes of AD, our study examined the roles of three types of skin antigen-presenting cells (APCs) in inducing distinct inflammatory responses in AD pathogenesis, utilizing animal models and genetically deficient mice. Our findings revealed that epidermal Langerhans cells primarily recognize allergens, induce Th2 inflammation, and promote IgE production. Nlrp3 contributes to macrophage activation by the AD lesion microbiota, driving Th17 inflammation and IgG1 production. The STING pathway facilitates dendritic cell activation, exacerbates the overall inflammatory process across mixed immune endotypes of AD, and the production of IgG2a and IgG1. In summary, our study conducted a comprehensive analysis of the upstream key antigen-presenting cells and their regulatory pathways that contribute to the progression of AD-associated immune endotypes. This research provides valuable insights into upstream mechanisms for controlling AD mixed inflammatory processes and offers strategic directions for developing combination therapies targeting multiple inflammatory pathways.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"188 ","pages":"Article 106850"},"PeriodicalIF":2.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear-localized SIRT1 inhibits apoptosis via deacetylating p53","authors":"Lin Cheng ,&nbsp;Ge Wu ,&nbsp;Wei Yao ,&nbsp;Kangrong Deng ,&nbsp;Chunsun Zhang ,&nbsp;Tongsheng Chen","doi":"10.1016/j.biocel.2025.106841","DOIUrl":"10.1016/j.biocel.2025.106841","url":null,"abstract":"<div><div>The function of silencing information regulator 1 (SIRT1) in promoting or inhibiting apoptosis remains a subject of debate. Here, we aim to evaluate the roles of nuclear-localized SIRT1 in STS/DOX-induced apoptosis. Silencing nuclear-localized SIRT1 significantly enhanced STS/DOX-induced apoptosis, while overexpression of nuclear-localized SIRT1 markedly inhibited STS/DOX-induced process, demonstrating the anti-apoptotic ability of the nuclear-localized SIRT1. Critically, silencing p53 compromised the anti-apoptotic function of nuclear-localized SIRT1, thereby underscoring the essential role of p53 in mediating SIRT1's anti-apoptotic capability. Western blot analysis further revealed that wild-type SIRT1 robustly downregulated Ac-p53 expression to inhibit apoptosis, whereas a deacetylase-defective mutant of SIRT1 (SIRT1^H363Y) markedly upregulated Ac-p53 to promote apoptosis. Fluorescence resonance energy transfer (FRET) analyses for the cells co-expressing nuclear-localized SIRT1-CFP and p53-YFP showed that STS enhanced the direct interaction between SIRT1 and p53 in nucleus, suggesting that the nuclear-localized SIRT1 directly interacts with p53 to deacetylate p53, thus inhibiting apoptosis. On the contrary，overexpression of cytoplasm-localized SIRT1 markedly promoted STS/DOX-induced apoptosis, firmly demonstrating the pro-apoptotic ability of the cytoplasm-localized SIRT1. These results firmly demonstrate a notion that nuclear-localized SIRT1 inhibits apoptosis via deacetylating p53.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106841"},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substrate stiffness modulates osteogenic differentiation of BMMSCs via the hedgehog signaling pathway","authors":"Chengyang Sun ,&nbsp;Mengying Jin ,&nbsp;Ying Lian ,&nbsp;Aodi Jiang ,&nbsp;Hongfeng Zhai","doi":"10.1016/j.biocel.2025.106840","DOIUrl":"10.1016/j.biocel.2025.106840","url":null,"abstract":"<div><div>Substrate stiffness is a critical biophysical cue regulating mesenchymal stem cell (MSC) fate, yet the underlying mechanisms remain incompletely understood. Here, we investigated how substrate stiffness modulates the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and the involvement of the Hedgehog (Hh) signaling pathway in this process. Polydimethylsiloxane (PDMS) substrates with tunable stiffness (soft: 32.73 ± 3.74 kPa; medium: 57.59 ± 5.65 kPa; stiff: 147.4 ± 11.04 kPa) were fabricated and functionalized with arginine-glycine-aspartic acid (RGD) peptides to mimic the mechanical microenvironment of bone tissue. BMMSCs cultured on stiff substrates exhibited enhanced cell spreading and proliferation compared to those on soft substrates. Osteogenic induction experiments revealed that stiff substrates significantly upregulated alkaline phosphatase (ALP) expression and calcium nodule formation after 7 and 21 days, respectively. Mechanistically, the Hh pathway was activated on stiff substrates at day 3. Inhibition of Hh signaling using GANT61 impeded stiffness-induced effects, reducing cell spreading, proliferation, and osteogenic differentiation. These findings demonstrate that substrate stiffness promotes BMMSCs osteogenesis in a Hh signaling-dependent manner, providing new insights into the mechanobiology of bone regeneration and informing the design of stiffness-optimized biomaterials for tissue engineering applications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106840"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ERO1A by TCF21 curbs aerobic glycolysis and enhances immune recognition in lung adenocarcinoma","authors":"Xiaoyu Zheng,&nbsp;Bin Jiang,&nbsp;Yingchun Zhang,&nbsp;Shigao Ye,&nbsp;Yongchun Liu","doi":"10.1016/j.biocel.2025.106831","DOIUrl":"10.1016/j.biocel.2025.106831","url":null,"abstract":"<div><h3>Background</h3><div>Among the many malignancies, lung adenocarcinoma (LUAD) is a top global health and life risk. The focus of this research is to explore how the TCF21/ERO1A pathway influences the immune escape mechanisms triggered by aerobic glycolysis in LUAD.</div></div><div><h3>Methods</h3><div>After downloading mRNA expression data from TCGA-LUAD and conducting differential expression analysis, we identified our target mRNA based on literature review. We used the hTFtarget database to forecast the upstream transcription factor (TF) of the target mRNA, and their binding relationship was verified through dual-luciferase experiments. Gene set enrichment analysis (GSEA) was performed on the target gene to probe its impact on LUAD-associated signaling pathways. qRT-PCR was used to detect the expression of ERO1A, TCF21, and PD-L1 mRNA. Western blot was employed to measure the expression levels of glycolysis-related proteins (SLC2A1, HK2, LDHA) and PD-L1 protein. Extracellular acidification rate and oxygen consumption rate were evaluated using a Seahorse metabolic analyzer. The apoptosis of CD8⁺ T cells and the activation status of CD8⁺ T cells were detected by flow cytometry. We also conducted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay to assess the cytotoxicity of natural killer cells against LUAD cells.</div></div><div><h3>Results</h3><div>High expression levels of ERO1A were observed in LUAD tissues and cells. GSEA identified a notable association of ERO1A with glycolytic processes and tumor immune evasion pathways. The depletion of ERO1A deeply impaired the glycolytic capacity, immune evasion abilities, and PD-L1 expression in LUAD cells, as validated by both cellular and molecular experiments. ERO1A induced immune evasion in LUAD cells via the upregulation of PD-L1. TCF21, an upstream regulator of ERO1A, was found to be downregulated in LUAD. Dual-luciferase assays also provided evidence for the specific binding of ERO1A to TCF21. Recovery experiments showed TCF21 curbed the stimulatory effect of glycolysis on the immune evasion of LUAD cells by suppressing ERO1A expression.</div></div><div><h3>Conclusion</h3><div>TCF21 directs its action towards ERO1A, thereby inhibiting the glycolysis-mediated promotion of immune evasion in LUAD cells. As such, the TCF21/ERO1A axis could be harnessed as a therapeutic target and a prognosis marker in LUAD.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"187 ","pages":"Article 106831"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Towards tailored exosomes: The exosomal tetraspanin web contributes to target cell selection” [Intern. J. Biochem. Cell Biol., 44/9 (2012) 1574–1584]","authors":"Sanyukta Rana ,&nbsp;Shijing Yue ,&nbsp;Daniela Stadel ,&nbsp;Margot Zöller","doi":"10.1016/j.biocel.2025.106824","DOIUrl":"10.1016/j.biocel.2025.106824","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106824"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Inhibition of M2 macrophage-mediated mesenchymal stem cell migration: Boldine attenuates elbow heterotopic ossification” [Int. J. Biochem. Cell Biol. 185 (2025) 106787]","authors":"Fengteng Shen ,&nbsp;Yansong Chen ,&nbsp;Zhikun Xu ,&nbsp;Wei Wang ,&nbsp;Guofang Chen ,&nbsp;Fusheng Ye","doi":"10.1016/j.biocel.2025.106829","DOIUrl":"10.1016/j.biocel.2025.106829","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106829"},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purinosomes and lysosomes interact to maintain the purine pools","authors":"Yubing Liu ,&nbsp;Vidhi Pareek ,&nbsp;Dipankar Bhowmik ,&nbsp;Xin Zhang ,&nbsp;Stephen J. Benkovic","doi":"10.1016/j.biocel.2025.106830","DOIUrl":"10.1016/j.biocel.2025.106830","url":null,"abstract":"<div><div>Purines are the building blocks of DNA/RNA and hence essential metabolites. While the contributions of external purine salvage as well as the <em>de novo</em> purine biosynthesis (DNPB) have been widely studied, the contribution of lysosome mediated DNA/RNA digestion and external reabsorption into the cytosol remains unknown. Here, we address that question as well as the role of lysosome-mediated purine recycling and its coordination with DNPB in maintaining total purine pools in human cancer cell lines. By combining in-cell stable isotope incorporation assay with quantitative metabolomics we show: cellular uptake of external purines and their internal generation are equivalent; an upregulation in lysosome biogenesis that functions in response to purine deficiency caused by methotrexate (MTX) and lometrexol (LTX) treatment. This leads to increased RNA digestion as visualized by a newly developed intracellular RNA-FRET oligo assay. Interestingly, downregulation of lysosomal RNase activity through knockdown of RNAseT2 increased RNA accumulation and a compensating increase in DNPB.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106830"},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}