Cellular Oncology最新文献

{"title":"Expression of the zinc-finger transcription factor Osterix (SP7) in invasive breast cancer and its prognostic significance.","authors":"Behnaz Saidy, Laura Gull, Andrew G Hacker, Emad A Rakha, Andrew R Green, Ian O Ellis, Stewart G Martin, Sarah J Storr","doi":"10.1007/s13402-025-01062-9","DOIUrl":"10.1007/s13402-025-01062-9","url":null,"abstract":"<p><strong>Introduction: </strong>Osterix, encoded by SP7, is a transcription factor crucial in osteoblast differentiation and bone formation. While initially characterised in bone development, emerging evidence suggests its involvement in cancer, particularly breast cancer metastasis to bone.</p><p><strong>Methods: </strong>Osterix protein expression was evaluated in 1340 early-stage invasive breast tumours by immunohistochemistry. Cytoplasmic and nuclear expression levels were assessed and associations with clinicopathological variables and patient survival determined. Additionally, SP7 mRNA expression was examined in the METABRIC cohort of patients. Gene set enrichment analysis (GSEA) was performed to explore the role of osterix in the hallmarks of cancer genesets.</p><p><strong>Results: </strong>Results revealed significant associations between reduced nuclear osterix protein expression and adverse clinicopathological features, including larger tumour size, higher grade, and poor Nottingham Prognostic Index. Low nuclear osterix protein expression was also linked to shorter breast cancer-specific survival and distant metastasis free survival, particularly in patients with HER2 positive tumours. No associations were found between SP7 mRNA expression and clinicopathological variables or survival outcomes. GSEA identified enrichment of genes involved in KRAS signaling in tumours with high SP7 expression.</p><p><strong>Conclusion: </strong>These data suggest that reduced nuclear expression of osterix is associated with poor clinical outcome of breast cancer patients and may be of clinical relevance.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1035-1045"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy.","authors":"Nan-Nan Ji, Shu-Ning Li, Ling Shao, Qing Li, Jun-Nv Xu, Yue-Can Zeng","doi":"10.1007/s13402-025-01065-6","DOIUrl":"10.1007/s13402-025-01065-6","url":null,"abstract":"<p><strong>Objective: </strong>Radioresistance is a common cause of poor radiation therapy effectiveness for non-small cell lung cancer. Finding molecular targets or methods to enhance radiosensitivity or overcome radioresistance is crucial. This study aimed to investigate the effects of MDMX on modulating radiosensitivity in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).</p><p><strong>Methods: </strong>The expression of MDMX and its correlation with radiotherapy response were analyzed in 101 LUAD and LUSC patient samples. LUAD and LUSC cell lines (A549, SK-MES-1) and their radioresistant counterparts (A549R, SK-MES-1R) were used to assess the effects of MDMX and P53 on radiosensitivity through autophagy by using molecular assays and animal models.</p><p><strong>Results: </strong>The expression of MDMX was decreased, but the autophagy was enhanced in radioresistant LUAD and LUSC cells. Overexpression of MDMX inhibited P53 activity, leading to autophagy suppression and increasing radiosensitivity. In contrast, P53 upregulation counteracted the effects of MDMX, resulting in increasing autophagy and radioresistance. The higher MDMX expression was associated with improved radiotherapy response and prolonged overall survival in LUAD and LUSC cells. The 5-year survival rate was 93.62% in the low MDMX expression group and 98.11% in the high MDMX expression group (P < 0.01).</p><p><strong>Conclusion: </strong>MDMX enhances LUAD and LUSC radiosensitivity by downregulating P53-mediated autophagy. High MDMX expression correlated with better clinical outcomes, suggesting that MDMX could be a potential biomarker for predicting radiotherapy response and prognosis in LUAD and LUSC patients.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1067-1088"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.","authors":"Hayam Hamdy, Chang Shen, Jiashun Xu, Die Fan, Yiwen Zhang, Hui Li, Yonglong Wei, Jianwei Sun","doi":"10.1007/s13402-025-01064-7","DOIUrl":"10.1007/s13402-025-01064-7","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, associated with viral hepatitis, alcohol consumption, and non-alcoholic fatty liver disease. Hepatocyte nuclear factor 4 alpha (HNF4α), a crucial transcription factor for liver function (glucose and lipid metabolism, bile acid homeostasis, and cellular differentiation), is often dysregulated in HCC progression. This review provides a comprehensive overview of the role of HNF4α in hepatic oncogenesis, providing novel inshight into its regulatory effects on epithelial-mesenchymal transition (EMT), metabolic alterations (including the Warburg effect), cell cycle control, and tumor microenvironment. We also discuss therapeutic strategies targeting HNF4α focusing on restoring metabolic balance and inducing apoptosis. This integrated analysis advances our understanding of HNF4α's contribution to HCC and may pave the way for the development of targeted therapies (Fig. 1).</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"885-897"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of lipopolysaccharide (LPS) expression in breast cancer cells.","authors":"Noel F C C de Miranda, Vincent T H B M Smit, Manon van der Ploeg, Jelle Wesseling, Jacques Neefjes","doi":"10.1007/s13402-025-01071-8","DOIUrl":"10.1007/s13402-025-01071-8","url":null,"abstract":"<p><p>The relationship between bacterial activity and tumorigenesis has gained attention in recent years, complementing the well-established association between viruses and cancer. A recent study employed immunodetection of lipopolysaccharide (LPS) to demonstrate the presence of intracellular bacteria within cancer cells across various cancer types, including breast cancer. The authors proposed that these bacteria might play a role in tumor development. We sought to replicate these findings using the same experimental methods on an independent cohort of breast cancer cases. Our analysis of 129 samples revealed no evidence of LPS expression within cancer cells. Instead, LPS immunoreactivity was observed in ducts or immune cells, specifically macrophages, as expected. These discrepancies in LPS immunodetection warrant caution in interpreting the original findings, and further research is needed to clarify the potential role of intracellular bacteria in cancer development.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1123-1126"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State of the art in CAR-based therapy: In vivo CAR production as a revolution in cell-based cancer treatment.","authors":"Abdolreza Esmaeilzadeh, Kaveh Hadiloo, Sara Yaghoubi, Masoud Hassanzadeh Makoui, Parsa Mostanadi","doi":"10.1007/s13402-025-01056-7","DOIUrl":"10.1007/s13402-025-01056-7","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) therapy has successfully treated relapsed/refractory hematological cancers. This strategy can effectively target tumor cells. However, despite positive outcomes in clinical applications, challenges remain to overcome. These hurdles pertain to the production of the drugs, solid tumor resistance, and side effects related to the treatment. Some cases have been missed during the drug preparation due to manufacturing issues, prolonged production times, and high costs. These challenges mainly arise from the in vitro manufacturing process, so reevaluating this process could minimize the number of missed patients. The immune cells are traditionally collected and sent to the laboratory; after several steps, the cells are modified to express the CAR gene before being injected back into the patient's body. During the in vivo method, the CAR gene is introduced to the immune cells inside the body. This allows for treatment to begin sooner, avoiding potential failures in drug preparation and the associated high costs. In this review, we will elaborate on the production and treatment process using in vivo CAR, examine the benefits and challenges of this approach, and ultimately present the available solutions for incorporating this treatment into clinical practice.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"859-883"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual blockage of P-cadherin and c-Met synergistically inhibits the growth of head and neck cancer.","authors":"Lihua Liu, Chan Oh, Mi Ae Lim, Sicong Zheng, Yudan Piao, Sun Ohm, Yujuan Shan, Shuyu Piao, Shan Shen, Young Il Kim, Ho-Ryun Won, Jae Won Chang, Min-Gyu Kim, Doh Hoon Kim, Ji Won Kim, Seung-Nam Jung, Bon Seok Koo","doi":"10.1007/s13402-025-01061-w","DOIUrl":"10.1007/s13402-025-01061-w","url":null,"abstract":"<p><strong>Purpose: </strong>P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanisms underlying its function.</p><p><strong>Methods: </strong>We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA), The Chungnam National University Hospital (CNUH) cohort and Gene Expression Omnibus (GEO) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models.</p><p><strong>Results: </strong>P-cadherin was significantly overexpressed in tumor samples compared to normal samples in the TCGA-HNSCC and CNUH-HNSCC cohorts. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functions as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 or c-Met siRNA resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone.</p><p><strong>Conclusion: </strong>Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be an effective approach for treating HNSCC.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1019-1033"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pericytes in hematogenous metastasis: mechanistic insights and therapeutic approaches.","authors":"Shuo Xu, Hong Zhang, Yu Tian","doi":"10.1007/s13402-025-01073-6","DOIUrl":"10.1007/s13402-025-01073-6","url":null,"abstract":"<p><p>Metastasis, the leading cause of cancer-related deaths, underscores the critical need to understand its regulatory mechanisms to improve prevention and treatment strategies for late-stage tumors. Hematogenous dissemination is a key route of metastasis. However, as the gatekeeper of vessels, the role of pericytes in hematogenous metastasis remains largely unknown. In this review, we comprehensively explore the contributions of pericytes throughout the metastatic cascade, particularly their functions that extend beyond influencing tumor angiogenesis. Pericytes should not be perceived as passive bystanders, but rather as active participants in various stages of the metastatic cascade. Pericytes-targeted therapy may provide novel insights for preventing and treating advanced-stage tumor.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"921-941"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embracing cancer immunotherapy with manganese particles.","authors":"Ali Moosavi Zenooz, Majid Eterafi, Soheil Azarmi Giglou, Elham Safarzadeh","doi":"10.1007/s13402-025-01070-9","DOIUrl":"10.1007/s13402-025-01070-9","url":null,"abstract":"<p><p>A substance integral to the sustenance and functionality of virtually all forms of life is manganese (Mn), classified as an essential trace metal. Its significance lies in its pivotal role in facilitating metabolic processes crucial for survival. Additionally, Mn exerts influence over various biological functions including bone formation and maintenance, as well as regulation within systems governing immunity, nervous signaling, and digestion. Manganese nanoparticles (Mn-NP) stand out as a beacon of promise within the realm of immunotherapy, their focus honed on intricate mechanisms such as triggering immune pathways, igniting inflammasomes, inducing immunogenic cell death (ICD), and sculpting the nuances of the tumor microenvironment. These minuscule marvels have dazzled researchers with their potential in reshaping the landscape of cancer immunotherapy - serving as potent vaccine enhancers, efficient drug couriers, and formidable allies when paired with immune checkpoint inhibitors (ICIs) or cutting-edge photodynamic/photothermal therapies. Herein, we aim to provide a comprehensive review of recent advances in the application of Mn and Mn-NP in the immunotherapy of cancer. We hope that this review will display an insightful view of Mn-NPs and provide guidance for design and application of them in immune-based cancer therapies.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"899-920"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LILRB1 enhances the progression of diffuse large B-cell lymphoma through the CREB-SORBS3 pathway.","authors":"Liyuan Cao, Hanqing Zhao, Xuanyi Zhou, Jin Yuan, Lietao Weng, Zhuo Yu, Junke Zheng, Chiqi Chen","doi":"10.1007/s13402-025-01060-x","DOIUrl":"10.1007/s13402-025-01060-x","url":null,"abstract":"<p><strong>Purpose: </strong>Although 60-70% of diffuse large B-cell lymphoma (DLBCL) patients can be cured with the current standard of chemotherapy and immunotherapy, the remaining patients experience treatment resistance and have poor clinical outcomes. More effective strategies are needed for the DLBCL treatment.</p><p><strong>Methods: </strong>Databases of clinical patients were analyzed to investigate potential functions of leukocyte immunoglobulin-like receptor B1 (LILRB1) in DLBCL. Short hairpin RNAs were used for validation of in vitro and in vivo function of LILRB1 in DLBCL. RNA-seq was applied to explore potential mechanism, western blot and chromatin immunoprecipitation techniques were used to characterize the underlying signaling of CREB-SORBS3 pathway.</p><p><strong>Results: </strong>We found that LILRB1 was highly expressed in DLBCL cells and was adversely correlated with the overall survival of DLBCL patients. Knockdown of LILRB1 effectively inhibited the proliferation of DLBCL cells both in vitro and in vivo. Mechanistically, LILRB1 upregulated CREB/CREB phosphorylation and transactivated SORBS3 expression to maintain DLBCL cell proliferation and tumorigenicity.</p><p><strong>Conclusion: </strong>In this work, we revealed that LILRB1 was highly expressed in DLBCL cells and was negatively correlated with patient survival. Furthermore, we found that the LILRB1-CREB-SORBS3 pathway played a role in maintaining the proliferation of DLBCL cells. These data suggest that LILRB1 might be a potential target for the treatment of DLBCL.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1005-1018"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts and metabolic reprogramming predict pathologic response to neoadjuvant PD-1 blockade in resected non-small cell lung cancer.","authors":"Jiaqi Zhao, Maolin Liu, Chongmei Zhu, Zhuolin Li, Zuhui Liu, Dilimulati Abulizi, Siqing Liu, Xin Wang, Haoxian Yang, Xue Hou","doi":"10.1007/s13402-025-01067-4","DOIUrl":"10.1007/s13402-025-01067-4","url":null,"abstract":"<p><strong>Purpose: </strong>Immunotherapy has transformed the neoadjuvant treatment landscape for patients with resectable locally advanced non-small cell lung cancer (NSCLC). However, a population of patients cannot obtain major pathologic response (MPR) and thus benefit less from neoadjuvant immunotherapy, highlighting the need to uncover the underlying mechanisms driving resistance to immunotherapy.</p><p><strong>Methods: </strong>Two published single-cell RNA sequencing (scRNA-seq) datasets were used to analyze the subsets of cancer-associated fibroblasts (CAFs) and T cells and functional alterations after neoadjuvant immunotherapy. The stromal signature predicting ICI response was identified and validated using our local cohort with stage III NSCLC receiving neoadjuvant immunotherapy and other 4 public ICI transcriptomic cohorts.</p><p><strong>Results: </strong>Non-MPR tumors showed higher enrichment of CAFs and increased extracellular matrix deposition than MPR tumors, as suggested by bioinformatic analysis. Further, CAF-mediated immune suppression may involve reciprocal interactions with T cells in addition to a physical barrier mechanism. In contrast, MPR tumors demonstrated therapy-induced activation of memory CD8⁺ T cells into an effector phenotype. Additionally, neoadjuvant immunotherapy resulted in expansion of precursor exhausted T (Texp) cells, which were remodeled into an anti-tumor phenotype. Notably, we identified metabolic heterogeneity within distinct T cell clusters during immunotherapy. Methionine recycling emerged as a predictive factor for T-cell differentiation and a favorable pathological response. The stromal signature was associated with ICI response, and this association was validated in five independent ICI transcriptomic cohorts.</p><p><strong>Conclusion: </strong>These discoveries underscore the distinct tumor microenvironments in MPR and non-MPR patients and may elucidate resistance mechanisms to immunotherapy in NSCLC.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1105-1119"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}