JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Mitochondrial Ferritin Overexpression Attenuates Ferroptosis and Mitochondrial Dysfunction by Reducing VDAC1 to Relieve MI/RI-Induced Damage","authors":"Yong Yuan,&nbsp;Xiuqi Wang,&nbsp;Huaihuan Xu,&nbsp;Lanxiang Liu,&nbsp;Jichun Liu,&nbsp;Songqing Lai,&nbsp;Huang Huang","doi":"10.1111/jcmm.70650","DOIUrl":"https://doi.org/10.1111/jcmm.70650","url":null,"abstract":"<p>Ischaemic cardiomyopathy is becoming one of the most prevalent cardiovascular diseases among the global elderly population. However, the underlying molecular mechanisms remain incompletely understood. Our previous study demonstrated that VDAC1 plays a significant role in MI/RI. Furthermore, FTMT plays a pivotal role in iron metabolism. However, the precise molecular functions of VDAC1 and FTMT in MI/RI remain to be elucidated. In vitro H9c2 cells A/R and in vivo SD rat MI/RI models were constructed. The present study reports that VDAC1 levels were increased and FTMT levels were decreased in A/R. The overexpression of VDAC1 resulted in an exacerbation of the A/R-induced injury, characterised by an increase in oxidative stress, a reduction in the GSH/GSSG ratio, the formation of reactive oxygen species, elevated levels of lipid peroxidation, and the deposition of iron. In contrast, FTMT overexpression reversed these alterations and mitigated mitochondrial dysfunction by downregulating VDAC1, PTGS2 levels, upregulating GPX4 levels, inhibiting MPTP over-opening and stabilising MMP. Additionally, knockdown of VDAC1 alleviated A/R-induced ferroptosis. In vivo experiments showed that overexpression of FTMT improved cardiac function in rats, as evidenced by the reduction of MI/RI-induced serum CK-MB, LDH and Fe²⁺ content and the shrinkage of myocardial infarction area. Moreover, HE, DHE staining and TEM observations showed that the overexpression of FTMT ameliorated MI/RI-induced myocardial tissue and mitochondrial damage. Furthermore, the overexpression of FTMT was found to inhibit MI/RI-induced ferroptosis. In general, our study is the first to demonstrate that FTMT overexpression alleviates ferroptosis and mitochondrial dysfunction by regulating VDAC1, thereby reducing MI/RI injury.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8C7: A Fully Human Anti-PTGFRN Monoclonal Antibody-Drug Conjugate Inhibiting Tumour Growth of Mesothelioma and Paediatric Medulloblastoma Cell Lines","authors":"Jorge Marquez,&nbsp;Jianping Dong,&nbsp;Binbin Yue,&nbsp;Jun Hayashi,&nbsp;Chun Dong,&nbsp;Mitsuo Oshimura,&nbsp;Ginette Serrero","doi":"10.1111/jcmm.70665","DOIUrl":"https://doi.org/10.1111/jcmm.70665","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Antibody Drug Conjugates (ADCs) are attractive for developing cancer-targeted therapies, particularly for cancers with unmet needs. Identification of a druggable internalising cell-surface target enables the development of internalising monoclonal antibodies to deliver toxic payloads directly to the cancer cells. Using immunohistochemistry, we screened various non-cancerous and cancerous tissue sections to assess PTGFRN expression levels. We produced hybridoma lines that produce fully human antibodies against the PTGFRN extracellular domain. After screening, we conjugated the cytotoxic payload Duocarmycin to an antibody candidate and tested its efficacy in in vitro assays, as well as in vivo xenografted athymic nude mice. We showed that PTGFRN expression was undetectable in non-cancerous tissue samples and overexpressed in several patient-derived cancer tissue samples. We produced a hybridoma line that produces a fully human IgG1 (8C7) against PTGFRN. 8C7 binds to cell-surface PTGFRN, inducing endocytosis of PTGFRN. Direct conjugation of Duocarmycin to 8C7 resulted in an antibody-drug conjugate that showed high potency in in vitro and in vivo models for three PTGFRN-expressing cell lines examined, A431, DAOY, and MSTO, while it had no effect on PTGFRN-negative MDA-MB-231. 8C7-ADC administered via intraperitoneal injection to xenografted mice showed inhibition of tumour formation and growth with no effect on body weight and organ weights. These findings further validate PTGFRN as a target for antibody-drug conjugate development for cancers with unmet needs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian Gene NPAS2 Relieves Hypertrophic Scar Formation via CDC25A-Mediated Fibroblasts Activity","authors":"Pei Wei,&nbsp;Yongqiang Xiao,&nbsp;Zhaorong Xu,&nbsp;Xiaodong Chen,&nbsp;Qiong Jiang,&nbsp;Yu Fu,&nbsp;Jianji Yan,&nbsp;Zhaohong Chen,&nbsp;Pengfei Luo,&nbsp;Huazhen Liu","doi":"10.1111/jcmm.70643","DOIUrl":"https://doi.org/10.1111/jcmm.70643","url":null,"abstract":"<p>Neuronal PAS domain protein 2 (NPAS2) is critical in tissue fibrosis. Hypertrophic scars (HTS), a form of skin fibrosis, are characterised by excessive myofibroblast proliferation and abnormal extracellular matrix (ECM) deposition. However, whether NPAS2 contributes to skin fibrosis and the development of HTS remains unclear. In this study, the expression of NPAS2 between normal skin and hypertrophic scars (HTS) was assessed using RT-qPCR and immunohistochemistry (IHC). Human dermal fibroblasts (HDFs) and HTS-derived fibroblasts (HTS-Fs) were isolated from normal skin and HTS, respectively. NPAS2 was knocked down in HTS-Fs and overexpressed in HDFs via gene transfection. Cell proliferation and migration of transfected HTS-Fs and HDFs were analysed using flow cytometry, CCK-8 and transwell assays. The expressions of NPAS2, CLOCK, BMAL1, COL I, COL III, α-SMA and CDC25A were evaluated by western blotting and RT-qPCR. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) identified the regulatory effect of NPAS2 on CDC25A. In vivo, an 8 × 8 mm full-thickness skin defect was created on the tail of SD rats, with viral particles (1 × 107) of r-plenR-sh-NPAS2 or r-plenR-NPAS2-NC injected subcutaneously at the wound edges weekly. Tissue samples, histopathological analyses and photographs were taken until the wound healed completely. The results indicated that NPAS2 was significantly upregulated in HTS. The proliferation, migration, and expression of COL I, COL III, and α-SMA were higher in HDFs overexpressing NPAS2 than those of HDFs themselves. In contrast, the behaviours mentioned above of HTS-Fs knocking down NPAS2 were lower than that of HTS-Fs. Mechanistically, the migration and proliferation promoting effect of NPAS2 was mediated by the binding of NPAS2 to the E-like-box of CDC25A. In vivo, compared with the r-plenR-NPAS2-NC group, the re-epithelialised regions of r-plenR-sh-NPAS2 were pink, flat and as large as the initial wound. In addition, their dermal structures were similar to skin and possessed loose and regular collagen arrangement which was parallel to the epidermis. Take together, these findings suggested that compared with HDFs, NPAS2 was upregulated in HTS-Fs. NPAS2 promoted the activation of HDFs, which is characterised by stronger proliferation and migration and the higher level of α-SMA, COL I and COL III. In which, the proliferation and migration effects of NPAS2 were mediated by CDC25A. Furthermore, NPAS2 knocked down in rat tail wounds inhibited the HTS formation. Therefore, NPAS2 may serve as a potential therapeutic target for HTS in the future.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of COG133 on Carbon Tetrachloride-Induced Acute Liver Injury: Modulation of Inflammation, Apoptosis and Sphingolipid Metabolism","authors":"Mutay Aslan,&nbsp;Bürke Çırçırlı,&nbsp;Aleyna Öztüzün,&nbsp;Hazal Tuzcu,&nbsp;Çağatay Yılmaz,&nbsp;Tuğçe Çeker,&nbsp;Gülsüm Özlem Elpek","doi":"10.1111/jcmm.70677","DOIUrl":"https://doi.org/10.1111/jcmm.70677","url":null,"abstract":"<p>Acute liver hepatotoxicity, characterised by inflammation, apoptosis and metabolic dysfunction, is often caused by drug-induced toxic events. This study evaluated the protective effects of COG133, a synthetic peptide derived from apolipoprotein E (ApoE), against carbon tetrachloride (CCl₄)-induced liver damage, focusing on inflammation, apoptosis and sphingolipid metabolism. An acute hepatotoxicity model was established in rats utilising CCl₄, with co-administration of COG133 at varying doses. Histological analyses, immunostaining, messenger RNA (mRNA)/protein quantification, flow cytometry and mass spectrometry were employed to assess necroinflammation, apoptosis and sphingolipid levels. Cell viability assays and morphological evaluations were conducted on rat hepatocytes and hepatic stellate cells (HSC-T6) to evaluate the protective effects of COG133. COG133 reduced liver damage, necroinflammation and apoptosis, restoring cell viability and lowering markers of inflammation, fibrosis and oxidative stress, including tumour necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (NOS2), interleukin-1 beta (IL-1β), transforming growth factor-beta (TGF-β) and collagen type I (Col-1). Immunostaining and molecular analyses confirmed these effects. Sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels were partially restored, while ceramide (CER) levels remained reduced in COG133-treated groups. COG133 protects against CCl₄-induced liver injury by reducing inflammation, apoptosis and morphological damage, with partial restoration of sphingolipid metabolism. These findings support its potential as a novel therapeutic agent for acute liver injury.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signalling Network Analysis of Blood Mononuclear Cells From Clinical Samples by Bivariate Correlation","authors":"David Kaplan,&nbsp;Hillard M. Lazarus,&nbsp;Jason Valent,&nbsp;Faiz Anwer,&nbsp;Sandra Mazzoni,&nbsp;Christy Samaras,&nbsp;Louis Williams,&nbsp;Meghan Nakashima,&nbsp;Mazen Hanna,&nbsp;Shahzad Raza,&nbsp;Eric Christian,&nbsp;Jack Khouri","doi":"10.1111/jcmm.70550","DOIUrl":"https://doi.org/10.1111/jcmm.70550","url":null,"abstract":"<p>Signalling networks have been assessed in blood cells by assessing individual phosphoantigens. We considered the possibility that bivariate correlations involving a series of signalling molecules could be used to delineate functional signalling networks in cells from clinical samples. Here, we describe a novel approach to signalling network analysis using enhanced flow cytometry to provide increased resolving power and restricted-dimensional cytometry which simplifies the analysis so that the precision of the analysis is optimised. This approach has been validated in short-term cultures by recapitulating known tenets of two distinct pathways. Additionally, new findings from our unique approach provide both expanded and nuanced views of signalling circuits. Applying our technology platform to blood mononuclear cells from patients with plasma cell disorders, we identified cell-type specific features of signalling pathways by distinct patterns of bivariate correlations. The intermolecular relationships between signalling analytes provide a description of the signalling network in blood cells from clinical samples. Consequently, our approach has the potential to assess how the blood mononuclear cell-type specific signalling network affects pathophysiology and pathogenesis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70550","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights From Amniotic and Umbilical Cord Mesenchymal Stem Cells in Wound Healing","authors":"Nong-er Shen,&nbsp;Yue Wu,&nbsp;Kaichuang Yang,&nbsp;Xiuling Xv,&nbsp;Gang Lu,&nbsp;Ruolang Pan,&nbsp;Yang Jin","doi":"10.1111/jcmm.70679","DOIUrl":"https://doi.org/10.1111/jcmm.70679","url":null,"abstract":"<p>Skin repair is a complex physiological process that involves the coordinated actions of various cell types. This study examines the distinct roles of amniotic mesenchymal stem cells (A-MSCs) and umbilical cord mesenchymal stem cells (UC-MSCs) in skin healing using a mouse model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed significant differences in gene expression between A-MSCs and UC-MSCs. Specifically, A-MSCs exhibited upregulation of genes associated with extracellular matrix (ECM) organisation and cell migration, thereby enhancing their tissue remodelling capabilities. In contrast, UC-MSCs demonstrate increased expression of genes involved in angiogenesis and anti-inflammatory responses, highlighting their role in creating a favourable healing environment. These findings highlight the unique therapeutic potentials of A-MSCs and UC-MSCs in skin repair strategies. Although MSCs hold promise in regenerative medicine, challenges such as optimal cell selection and modulation of the inflammatory microenvironment remain to be addressed. Our research emphasises the need for continued research related to properties of MSCs to refine therapeutic approaches for effective wound healing.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Optical Genome Mapping for the Detection of Tyrosine Kinase Gene Fusions in Myeloid/Lymphoid Neoplasms","authors":"Justine Vanhevel,&nbsp;Katrina Rack,&nbsp;Geneviève Ameye,&nbsp;Hayat Mokrani,&nbsp;Jolien De Bie,&nbsp;Lucienne Michaux,&nbsp;Barbara Dewaele","doi":"10.1111/jcmm.70640","DOIUrl":"https://doi.org/10.1111/jcmm.70640","url":null,"abstract":"<p>Myeloid/Lymphoid Neoplasms with eosinophilia and involvement of Tyrosine Kinase gene fusions (MLN-TK) is a WHO disease category including a diverse group of malignancies characterised by recurrent genomic rearrangements of tyrosine kinase (TK) genes such as <i>PDGFRA</i>, <i>PDGFRB</i>, <i>FGFR1</i>, <i>JAK2</i>, <i>ETV6</i> and <i>FLT3</i>. Identification of these TK rearrangements is important for the accurate diagnosis of MLN-TK and allows targeted therapy with TK inhibitors. In this study, we validated the use of optical genome mapping (OGM) retrospectively by analysing 11 samples from 10 cases with suspected or known TK rearrangements, previously analysed by current standard of care (SOC) methodologies, i.e., chromosome banding analysis (CBA), FISH and/or PCR-based techniques. In six abnormal cases, OGM was able to detect the rearrangements previously determined by SOC methods. Furthermore, OGM identified the fusion partner in the <i>JAK2</i>- and <i>PDGFRB</i>-rearranged cases and elucidated the mechanism underlying the <i>BCR::FGFR1</i> and <i>ETV6::SYK</i> rearrangement. In two cases with a normal karyotype, OGM detected two cryptic <i>FIP1L1::PDGFRA</i> and <i>TNIP1::PDGFRB</i> rearrangements. In the two remaining cases, no abnormalities were detected either by OGM or SOC methods. We demonstrate that OGM is a valid technique for the diagnostic workflow of MLN-TK, able to detect TK rearrangements and to identify unknown TK fusion partners.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotine Exacerbates Arrhythmogenesis in Rabbit Right Ventricular Outflow Tract Triggered by Chronic Obstructive Pulmonary Disease","authors":"Chao-Shun Chan,&nbsp;Feng-Zhi Lin,&nbsp;Yao-Chang Chen,&nbsp;Satoshi Higa,&nbsp;Shih-Ann Chen,&nbsp;Yi-Jen Chen","doi":"10.1111/jcmm.70664","DOIUrl":"https://doi.org/10.1111/jcmm.70664","url":null,"abstract":"<p>Cigarette smoke includes nicotine that increases ventricular tachycardia (VT) risk. Chronic obstructive pulmonary disease (COPD) and right ventricular outflow tract (RVOT) constitute the primary risk factor and origin of VT, respectively. To investigate the arrhythmogenesis of nicotine in COPD, we employed tachypacing with or without H89, KN93 and KB-R7943 treatment, along with patch clamp experiments and Masson's trichrome staining in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. Following 20-Hz tachypacing and isoproterenol treatment, COPD RVOTs had a higher VT incidence than control RVOTs. Nicotine-treated COPD RVOTs had higher ventricular arrhythmogenesis than non-treated COPD RVOTs. VTs induced in COPD and nicotine-treated COPD RVOTs were suppressed by H89, KN93, or KB-R7943. COPD RVOT myocytes exhibited shorter action potentials than control RVOT myocytes; nicotine-treated COPD RVOT myocytes exhibited longer action potentials than COPD RVOT myocytes. Both COPD and nicotine-treated COPD myocytes had smaller L-type Ca²⁺ currents and larger NCX currents than control RVOT myocytes. Nicotine-treated COPD RVOT myocytes had larger late Na⁺ currents than control and COPD RVOT myocytes. COPD and nicotine-treated COPD RVOTs exhibited more fibrosis. Nicotine-treated COPD RVOTs had the highest level of fibrosis. COPD intensifies RVOT VT through electrical and structural remodelling and Ca²⁺ dysregulation through the activation of PKA, CaMKII and NCX signalling pathways. Nicotine further exacerbates VTs in the rabbit RVOT triggered by COPD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HEY1 promotes the development and metastasis of osteosarcoma through CD44/EGFR/FAK pathway","authors":"Yuhang Liu,&nbsp;Hao Zhang,&nbsp;Xinzeyu Yi,&nbsp;Zheng Wang,&nbsp;Aixi Yu","doi":"10.1111/jcmm.70042","DOIUrl":"https://doi.org/10.1111/jcmm.70042","url":null,"abstract":"<p>Osteosarcoma (OS) is a highly prevalent and deadly malignant tumour primarily affecting adolescents. However, the identification of new therapeutic targets remains an urgent need. The advent of bioinformatics technology has offered us a novel approach to screen key genes from diverse OS-related databases, thereby providing valuable insights into the mechanistic understanding of OS prognosis. In this study, we comprehensively integrated multiple databases to identify the crucial oncogene, HEY1, which exerts a significant impact on OS prognosis. Subsequently, we conducted a experimental validations to explore influence of HEY1 knockdown on OS cells. HEY1 exhibited significant overexpression in OS tissues and cells and its silencing resulted in a significant inhibition of proliferation. The interaction between HEY1 and CD44 was identified through transcriptome sequencing and mass spectrometry analysis. Additionally, our findings suggested that HEY1 could potentially influence the EGFR-FAK pathway. Further experiments established that HEY1 regulates the EGFR-FAK pathway via CD44, thereby influencing the biological phenotype of OS cells. These findings were subsequently validated using in vivo animal models. In summary, HEY1 demonstrated significant overexpression in both OS tissues and cells, exerting a substantial impact on the prognosis of OS.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-Derived LGALS9-P4HB Immune Interaction Promotes Metastasis in Gastric Cancer Through Enhanced Cell Proliferation and Lipid Metabolism","authors":"Xiaobin Zhu,&nbsp;Yating Zhang,&nbsp;Aiping Yu,&nbsp;Xiao Xiao","doi":"10.1111/jcmm.70661","DOIUrl":"https://doi.org/10.1111/jcmm.70661","url":null,"abstract":"<p>Metastasis remains the primary cause of mortality in gastric cancer patients; however, the underlying mechanisms driving this process remain incompletely understood. Here, we performed an integrated single-cell analysis of gastric cancer primary tumours and their corresponding liver and lymph node metastases to identify critical intercellular communication networks driving the metastatic process. Notably, gene expression analysis of metastatic tissues showed significant upregulation of cholesterol metabolism and PPAR signalling pathway (a nuclear receptor–mediated regulatory system that orchestrates lipid metabolism, adipogenesis and energy homeostasis) genes compared to primary tumours. Our analysis revealed that myeloid cell–derived Galectin-9 (LGALS9) and its receptor beta-subunit of prolyl 4-hydroxylase (P4HB) on epithelial cells constitute a previously uncharacterized ligand–receptor interaction involved in gastric cancer metastasis. Functional experiments confirmed that the activation of P4HB by LGALS9 significantly enhanced proliferation, epithelial-mesenchymal transition (EMT) and lipid metabolism in gastric cancer cells, while pharmacological inhibition of P4HB reversed these effects. Collectively, our findings establish the myeloid-derived LGALS9-P4HB interaction as a crucial mediator of gastric cancer metastatic colonisation through modulation of lipid metabolism, suggesting a potential therapeutic target for metastatic gastric cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}