JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Unmatched Cell Line Collections Are Not Optimal for Identification of PARP Inhibitor Response and Drug Synergies","authors":"Zoe Phan,&nbsp;Kristine J. Fernandez,&nbsp;C. Elizabeth Caldon","doi":"10.1111/jcmm.70845","DOIUrl":"https://doi.org/10.1111/jcmm.70845","url":null,"abstract":"<p>PARP inhibitors show great efficacy in <i>BRCA1</i>/<i>2-</i>mutated patients, but many preclinical studies, including combination therapies, fail to translate clinically, likely due to the limitations of preclinical models. This brief report aimed to identify appropriate cell line models to investigate PARP inhibitor sensitivity and synergies. An <i>in silico</i> study of cell line collections was performed to assess the correlation between <i>BRCA1/2</i> mutations and sensitivity to PARP inhibitor monotherapy or with platinum-based chemotherapy. Subsequently, we characterised an isogenic model containing <i>Brca1</i> and <i>Brca2</i> mutations and investigated treatment response. Using cell line collections, <i>BRCA1-</i> and <i>BRCA2-</i>altered cell lines were not associated with increased sensitivity to PARP inhibitors. Other factors, including high <i>PARP1</i> expression and low-level genome alterations, showed correlation with increased sensitivity to a PARP inhibitor. Furthermore, cell line collections did not reflect the improved patient outcomes arising from combination PARP inhibitor and platinum-based chemotherapy. In contrast, the ID8 isogenic model, with specific <i>Brca1</i> and <i>Brca2</i> mutations, reflected patient tumour-like responses to PARP inhibitor monotherapy and combination therapy. This study suggests exercising caution when using cell line collections as part of model selection when investigating PARP inhibitor sensitivity and synergy. Our data propose that using an isogenic preclinical model is more likely to accurately reflect patient tumour response. However, as this study was limited to a single isogenic model, further validation in additional systems will be required to broaden the scope of these observations.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110942","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":"Association of TRDMT1 Gene Polymorphisms With Neuroblastoma Susceptibility: Insights From a Case–Control Study","authors":"Mengzhen Zhang,&nbsp;Wenli Zhang,&nbsp;Chunlei Zhou,&nbsp;Jiaming Chang,&nbsp;Jiabin Liu,&nbsp;Lei Lin,&nbsp;Xinxin Zhang,&nbsp;Liping Chen,&nbsp;Jing He,&nbsp;Baowei Han","doi":"10.1111/jcmm.70848","DOIUrl":"https://doi.org/10.1111/jcmm.70848","url":null,"abstract":"<p>Neuroblastoma is the most common extracranial solid tumour in children, and genetic susceptibility plays a crucial role in its development. The impact of tRNA Dimethyltransferase 1 (TRDMT1), a primary methyltransferase catalysing 5-methylcytosine (m5C) RNA modification, on neuroblastoma susceptibility remains unexplored. We conducted a case–control study involving 402 neuroblastoma patients and 473 controls from Jiangsu, China. <i>TRDMT1</i> polymorphisms (rs7074891 T&gt;C, rs10904887 T&gt;C and rs2273734 C&gt;T) were genotyped via the TaqMan assay. Logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs), while stratification analysis and expression quantitative trait locus (eQTL) analysis were used to examine subgroup-specific effects and regulatory impacts. Additionally, clinical correlation analysis and survival analysis were performed on neuroblastoma datasets used to evaluate. The rs7074891 TC/CC genotype reduced neuroblastoma risk (adjusted OR = 0.75, 95% CI = 0.57–0.98, <i>p</i> = 0.036), especially in children aged ≤ 18 months and those with mediastinal-origin tumours. Conversely, the rs10904887 CC (adjusted OR = 1.73, 95% CI = 1.27–2.38, <i>p</i> = 0.0006) and rs2273734 TT genotypes (adjusted OR = 1.80, 95% CI = 1.09–2.97, <i>p</i> = 0.023) were associated with increased risk, with distinct subgroup-specific effects. Combined 1–3 risk genotypes further confirmed increased susceptibility (adjusted OR = 1.81, 95% CI = 1.38–2.37, <i>p</i> &lt; 0.0001), particularly in males and older children. eQTL analysis revealed that the rs7074891 C and rs10904887 C alleles increased <i>TRDMT1</i> expression, whereas the rs2273734 T allele decreased it. Elevated <i>TRDMT1</i> expression was correlated with poor prognosis and high-risk clinical features. <i>TRDMT1</i> polymorphisms are significantly associated with neuroblastoma susceptibility, providing insights into their genetic and epigenetic mechanisms and potential as biomarkers and therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110941","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":"CAPG Regulates Doxorubicin Resistance in Hepatocellular Carcinoma Cells via TGFB1/Smad/Nrf2 Signalling Pathway","authors":"Yue Shang,&nbsp;Jun Zhang,&nbsp;Tingting Liu","doi":"10.1111/jcmm.70847","DOIUrl":"https://doi.org/10.1111/jcmm.70847","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a common and deadly type of liver cancer with limited treatment options and a considerable issue with chemoresistance. This study investigates the role of the cytoskeleton-associated protein G (CAPG) gene in HCC and explores its expression, clinical relevance, as well as the molecular mechanisms on doxorubicin (Dox) resistance. Employing bioinformatics, immunohistochemistry, cell-based assays and animal models, we systematically explored CAPG's function in HCC. Our results demonstrated that CAPG was markedly upregulated in HCC tissues and cell lines compared to normal controls (***<i>p</i> &lt; 0.001). High CAPG expression was associated with poor overall survival (HR = 1.98, <i>p</i> &lt; 0.001) and unfavourable clinicopathological parameters, indicating its potential as a prognostic biomarker. Functional experiments indicated that CAPG knockdown significantly reduced viability and proliferation in Dox-resistant HCC cells (***<i>p</i> &lt; 0.01). Conversely, overexpression promoted resistance. Mechanistically, CAPG appears to modulate ferroptosis via the TGFB1/Smad2/NRF2 signalling pathway, as supported by GSEA analysis and subsequent molecular assays. In vivo, CAPG knockdown in combination with Dox treatment significantly inhibited tumour growth in nude mouse models (***<i>p</i> &lt; 0.01). These findings suggest that CAPG is a pivotal regulator of HCC progression and chemoresistance, offering a promising prognostic biomarker and combinatorial therapeutic target to overcome Dox resistance in clinical settings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110927","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":"Advances and Deep Insights Into Lactylation: Essential Roles in Cellular Regulation and Disease Association","authors":"Tong Pan,&nbsp;Can-can Du,&nbsp;Ying-jian Zhang,&nbsp;Zhen-long Liu","doi":"10.1111/jcmm.70810","DOIUrl":"https://doi.org/10.1111/jcmm.70810","url":null,"abstract":"<p>Proteins exert biological functions not only depending on abundance but also on regulation. Lactylation is an important novel post-translational modification (PTM) that can affect protein structure and function, playing a crucial role in signal transduction, gene expression and cellular metabolism. Lactylation participates in the progression of various diseases, such as tumours, heart failure, myocardial infarction, renal fibrosis and Alzheimer's disease. These studies suggest that lactylation may mediate metabolic reprogramming and enhance cellular plasticity, providing new entry points for developing therapeutic approaches. This review introduces the progress on various aspects of lactylation, including mechanisms, regulations and disease associations, aiming to provide valuable insights and inspiration for further exploration of protein modification networks.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110940","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":"Molecular Expression Differences in Specific Blood Mononuclear Cell-Types Identify Patients With AL Amyloidosis","authors":"David Kaplan,&nbsp;Eric Christian,&nbsp;Jason Valent,&nbsp;Faiz Anwer,&nbsp;Sandra Mazzoni,&nbsp;Christy Samaras,&nbsp;Louis Williams,&nbsp;Megan Nakashima,&nbsp;Shahzad Raza,&nbsp;Mazen Hanna,&nbsp;Hillard M. Lazarus,&nbsp;Jack Khouri","doi":"10.1111/jcmm.70850","DOIUrl":"https://doi.org/10.1111/jcmm.70850","url":null,"abstract":"<p>The diagnosis of AL amyloidosis is often challenging due to its systemic nature and heterogeneous clinical presentation. Current serological biomarkers for diagnosis and monitoring are not optimal. We have considered the possibility that mononuclear cell-type specific molecular expression can be used to develop blood-based biomarkers to diagnose and monitor patients with AL amyloidosis. Peripheral blood monocytes and CD4⁺ T cells from patients with documented AL amyloidosis or myeloma without amyloidosis were assessed by enhanced flow cytometric analysis for expression levels of 20 analytes chosen for the possibility that their expression levels may lead to diagnostic assays and biomarkers. We found definitive expression level differences for brain-derived neurotrophin factor (BDNF), calmodulin, and phospho-TBK1 in CD4⁺ T cells and for phospho-GSK3β in monocytes. Logistic regression and ROC analysis showed that BDNF in CD4⁺ T cells and heme oxygenase 1 in monocytes significantly distinguished between patients with myeloma versus patients with AL amyloidosis (AUC = 0.75). Additionally, we discovered remarkable differences in intermolecular associations between the samples from the two patient groups, suggesting the involvement of specific pathogenetic pathways. Our results demonstrate that mononuclear cell-type specific molecular expression may be useful for developing a diagnostic assay and biomarkers for patients with AL amyloidosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110939","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":"Secreted Frizzled-Related Protein 2 Promotes Osteogenic Differentiation and Bone Regeneration in Perthes Disease When Targeted by miR-106a-5p","authors":"Tianjiu Zhang,&nbsp;Jiafei Yang,&nbsp;Song Yu","doi":"10.1111/jcmm.70804","DOIUrl":"https://doi.org/10.1111/jcmm.70804","url":null,"abstract":"<p>Although the pathogenesis of Perthes disease remains unclear, the mechanism of bone regeneration in the defective femoral head is an area of particular interest. Improving understanding of the underlying mechanisms is essential for the development of an effective treatment for this condition. This study explored the roles of secreted frizzled-related protein 2 (SFRP2) and micro ribonucleic acid (miR)-106a-5p in the regulation of osteogenic differentiation (in vitro) and bone regeneration (in vivo). Cells were transfected with plasmids carrying the genes encoding SFRP2 and miR-106a-5p. Cell proliferation and apoptosis were evaluated using 5-ethynyl-2′-deoxyuridine staining, flow cytometry and the terminal deoxynucleotidyl transferase dUTP nick end-labelling assay. Osteogenic differentiation was identified using alkaline phosphatase and alizarin red S staining. Reverse transcription quantitative polymerase chain reaction and western blot were used to assess messenger ribonucleic acid and protein levels. The dual-luciferase reporter gene assay was used to confirm the targeting relationship between miR-106a-5p and SFRP2. Changes in bone structure were evaluated by morphological observation, micro-computed tomography and alkaline phosphatase staining. The findings showed that SFRP2 significantly increased cell proliferation and osteogenic differentiation and inhibited apoptosis of bone marrow mesenchymal stem and MC3T3-E1 cells. It upregulated the expression of PCNA, Bcl-2, ALP, Col1a1, Runx2, Osterix, Wnt3a, β-catenin, LRP5 and LRP6, and downregulated that of Bax. Negative regulation of SFRP2 by miR-106a-5p (via the Wnt/β-catenin pathway) could rescue the influence of the latter; this showed that SFRP2 is a target gene of miR-106a-5p.In conclusion, miR-106a-5p/SFRP2 may play a crucial role in bone regeneration in the defective femoral head and may be a potential therapeutic target in Perthes disease.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111016","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 Role of Radiotherapy After Full Course of Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis","authors":"Xiping Liang,&nbsp;Xu Deng,&nbsp;Kanglin Xie,&nbsp;Chaoyu Wang,&nbsp;Yao Liu","doi":"10.1111/jcmm.70822","DOIUrl":"10.1111/jcmm.70822","url":null,"abstract":"<p>Rituximab has improved response rates and overall survival in diffuse large B-cell lymphoma (DLBCL). Radiotherapy (RT) is an effective treatment modality for lymphomas. However, significant conceptual challenges, including the application in elderly patients, varying IPI scores and CR patients, remain regarding the current use of RT. We performed a systematic review comparing chemotherapy with RT to chemotherapy alone in patients with DLBCL. We estimated hazard ratios (HR) for OS, PFS and EFS using the proportional hazards model. Five articles involving 1364 patients met inclusion criteria. Patients undergoing consolidative RT had better OS (HR = 0.46, 95% CI 0.31–0.68), PFS (HR = 0.52, 95% CI 0.22–1.25) and EFS (HR = 0.42, 95% CI 0.20–0.90) compared to those who received no RT. But no benefit was shown in patients with achievement of CR. The protective effect of consolidation RT for patients with advanced IPI scores (HR = 0.46, 95% CI 0.31–0.68) and advanced stage (HR = 0.22, 95% CI 0.08–0.59) was shown. The consolidation RT showed a significantly longer PFS (HR = 0.50, 95% CI 0.26–0.94) but no significant benefit on OS in patients with bulky disease. There was also significantly better PFS in RT patients (HR = 0.67, 95% CI 0.49–0.92), but no significant benefit on OS in old age patients. RT act as an efficacious method for DLBCL following a full course of chemotherapy. However, no OS benefit was shown in patients with advanced IPI scores, bulky disease, CR and old age.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086257","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":"Amino Acid Restriction Impairs Human Endometrial Stromal Cell Decidualization and Is Rescued by Proline Supplementation","authors":"Chloe Jang,&nbsp;Cristiana Iosef,&nbsp;Stephen J. Renaud,&nbsp;Victor K. M. Han","doi":"10.1111/jcmm.70821","DOIUrl":"10.1111/jcmm.70821","url":null,"abstract":"<p>Decidualization is a critical process for successful pregnancy. It is characterised by the transformation of endometrial stromal cells into decidual cells that support embryo implantation and placental development. Maternal amino acid deficiency is linked to impaired decidualization, which can lead to pregnancy complications such as miscarriage, preeclampsia and fetal growth restriction. Halofuginone (HF), a synthetic alkaloid, induces nutritional stress by triggering the amino acid starvation response. This study investigated the effects of HF-induced nutritional stress and amino acid supplementation on decidualization of human endometrial stromal cells (HESCs). Exposure of HESCs to decidualization agents caused distinct morphological changes and expression of insulin-like growth factor binding protein-1 (IGFBP-1), indicative of successful decidualization. Treatment of HESCs with HF or leucine-deprived media inhibited the expression of key decidualization markers. Interestingly, supplementation with proline, but not leucine, rescued the inhibitory effects of HF on decidualization of HESCs. HF inhibited the expression of genes encoding growth factors crucial for decidualization, highlighting their sensitivity to amino acid availability, and disrupted transforming growth factor β-SMAD signalling, which was restored by proline supplementation. These findings highlight the essential role of amino acids, particularly proline, for proper decidualization and suggest potential therapeutic strategies for improved reproductive health.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075314","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":"Targeting CD19 CAR-T With MND Promoter Enhances Tumour Killing","authors":"Xiaomei Zhang,&nbsp;Xiaoyuan He,&nbsp;Yu Zhang,&nbsp;Jile Liu,&nbsp;Shujing Guo,&nbsp;Cuicui Lyu,&nbsp;Mingfeng Zhao","doi":"10.1111/jcmm.70843","DOIUrl":"10.1111/jcmm.70843","url":null,"abstract":"<p>Although Chimeric antigen receptor (CAR) T cell therapy has demonstrated a high remission rate in B cell acute lymphoblastic leukaemia, concerns regarding toxicity and disease recurrence remain. Different promoters can modulate the expression levels of CAR molecules on the cell surface. In this study, we systematically compared four distinct promoters (MND, MSCV, EF-1α and CMV). Our findings revealed that while these promoters exhibited similar characteristics, the MND promoter demonstrated superior viral packaging and transduction efficiency. Furthermore, it enhanced the anti-leukaemia efficacy by increasing the proportion of naïve T cells involved in the cytotoxic process.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075302","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":"HIF-1α Promotes the Confined Migration of Gastric Cancer Cells by Modulating Phosphatidylcholine Metabolism","authors":"Ming Zhou,&nbsp;Kanger Shen,&nbsp;Ziyi Huang,&nbsp;Qin Zhan,&nbsp;Jiayu Wang,&nbsp;Xiaozhe Mao,&nbsp;Tongguo Shi,&nbsp;Rui Li","doi":"10.1111/jcmm.70828","DOIUrl":"10.1111/jcmm.70828","url":null,"abstract":"<p>Confined migration (CM) is a key step in the process of cancer cell metastasis. However, the molecular mechanisms underlying CM in gastric cancer (GC) remain unclear. Here, we found that CM-GC cells had remarkable metastatic and antiapoptotic capacities. Moreover, we observed that HIF-1α was highly expressed in CM-GC cells. HIF-1α knockdown reversed the enhanced metastatic and antiapoptotic capacities of CM-GC cells in vitro and in vivo. Mechanistically, HIF-1α enhanced the metastatic and antiapoptotic capacities of CM-GC cells through phosphatidylcholine (PC) synthesis. Importantly, the addition of L-α-phosphatidylcholine (L-α-PC), a natural PC, markedly increased the metastatic and antiapoptotic capacities of GC cells, similar to CM GC cells. In addition, we observed that increased HIF-1α protein expression was positively correlated with the expression of CEPT1, a key enzyme of PC synthesis, in GC tissue samples. Furthermore, high expression of HIF-1α and CEPT1 in GC tissues predicted poor prognosis in patients with GC. Overall, our study supports the crucial role of HIF-1α in the CM of GC cells and provides novel therapeutic targets and strategies for metastatic GC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069662","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}