Cellular Oncology最新文献

{"title":"CAFs mediate carboplatin resistance in LUAD via CXCL12 secretion regulated by NF-κB activation.","authors":"Long Li, Xu Zhu, Zeyang Yang, Xuanyin Wang, Xianling Zeng, Lu Wang, Jiaming Ren, Jiangwei Wu, Qiaoling Zhang, Jing Xiao, Ying Zhang, Song Yang, Yuanhan Wang, Jian Zhang, Xinlei Liu, Siyuan Yang, Zhu Zeng, Jieheng Wu","doi":"10.1007/s13402-025-01106-0","DOIUrl":"https://doi.org/10.1007/s13402-025-01106-0","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer-associated fibroblasts (CAFs) are major constituents of the tumor microenvironment (TME) and have been associated with chemotherapeutic failure via different mechanisms. However, the CAFs inhibit chemotherapy mechanism in lung adenocarcinoma (LUAD) remains undetermined.</p><p><strong>Methods: </strong>Fibroblasts were isolated from tumor and normal lung tissues from patients with poorly differentiated LUAD (pCAFs), moderately differentiated LUAD (mCAFs), and normal fibroblasts (NFs). Then, the influence of these fibroblasts on carboplatin's cytotoxic effects on LUAD cell lines A549 and NCI-H1299 was assessed by measuring their IC₅₀ values. Furthermore, CXCL12 secretion and its role in chemotherapeutics were also evaluated.</p><p><strong>Results: </strong>The data revealed that pCAFs significantly inhibited apoptosis in LUAD cells and increased carboplatin IC₅₀ values. Furthermore, pCAFs secreted higher CXCL12 content than mCAFs and NFs. Moreover, in pCAFs, CXCL12 silencing enhanced carboplatin's cytotoxic effects, while NFs overexpressing CXCL12 inhibited carboplatin's efficacy. Mechanistically, pCAFs promote the secretion of CXCL12 by activating the NF-κB pathway, and CXCL12 binds to CXCR4 on LUAD cells, thereby promoting carboplatin resistance. Moreover, in the xenograft models, pCAFs were found to reduce carboplatin's cytotoxicity by CXCL12 secretion. Moreover, the analysis of the LUAD patient's tumor and peripheral blood sample indicated a correlation between lower differentiation and higher CXCL12 expression levels.</p><p><strong>Conclusion: </strong>This study revealed that LUAD-derived CAFs activate the NF-κB axis to secrete CXCL12, thereby weakening the carboplatin's killing effect on LUAD. Furthermore, poorly differentiated LUAD secreted more CXCL12. These findings indicate a novel strategy to enhance carboplatin's chemotherapeutic potential against LUAD.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a ¹⁷⁷Lu-labeled EphA2-targeting cyclic peptide combined with an HPK1 inhibitor for synergistic anti-tumor effects.","authors":"Meng-Jie Zhang, Yirong Chen, Caixia Zhang, Xiaofeng Bian, Xiangyang Zhang, Shijia Huang, Bowen Yang, Siyan Lu, Xueting Fu, Wei Zhao, Xu-Dong Kong, Shuli Zhao","doi":"10.1007/s13402-025-01105-1","DOIUrl":"https://doi.org/10.1007/s13402-025-01105-1","url":null,"abstract":"<p><strong>Purpose: </strong>Despite advancements in ¹⁷⁷Lu-based radiotherapy for cancer, its efficacy against refractory cold tumors remains limited. Targeted peptide-radionuclide conjugates (PRCs) combined with immunotherapy are emerging as promising theranostic strategies to maximize anti-tumor effectiveness.</p><p><strong>Methods: </strong>Cyclic peptide CEMJ4 was identified via phage selection, and further conjugated with DOTA and radiolabeled with ⁶⁸Ga for diagnostic imaging and ¹⁷⁷Lu for cancer therapy. The druggability was assessed by in vitro cell experiments, in vivo PET/CT imaging and biodistribution. Additionally, the feasibility of combining ¹⁷⁷Lu-DOTA-CEMJ4 with a hematopoietic progenitor kinase 1 inhibitor (HPK1i) was evaluated in B16F10 tumor-bearing mice, focusing on the anti-tumor immune response and tumor growth.</p><p><strong>Results: </strong>CEMJ4 exhibited high affinity for human erythropoietin-producing hepatocellular receptor A2 (EphA2; K_D = 0.3 ± 0.2 µM), a therapeutic target overexpressed in several solid tumors. Radiolabeled ⁶⁸Ga/¹⁷⁷Lu-DOTA-CEMJ4 specifically bound to EphA2-expressing B16F10 cells and tumor models, effectively inhibiting tumor growth. Notably, ¹⁷⁷Lu-induced T cell immunotoxicity was reversed by HPK1i, which modulated T cell dysfunction. Combining ¹⁷⁷Lu-DOTA-CEMJ4 with HPK1i significantly reduced tumor burden and increased tumor-infiltrating CD4⁺ T cells, CD8⁺ T cells, and M1 macrophages.</p><p><strong>Conclusion: </strong>This study identifies CEMJ4 as a promising peptide ligand for tumor-targeted radionuclide delivery and emphasizes the clinical potential of radionuclide therapy combined with immunotherapy in theranostics to enhance therapeutic precision and efficacy.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RACK1 attenuates pancreatic tumorigenesis by suppressing acinar-to-ductal metaplasia through inflammatory signaling modulation.","authors":"Wei Zhang, Tingting Jiang, Huiqing Zhang, Fang Wei, Xiaojia Li, Keping Xie","doi":"10.1007/s13402-025-01084-3","DOIUrl":"https://doi.org/10.1007/s13402-025-01084-3","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal malignancies with limited early diagnostic and therapeutic options. Although receptor for activated C kinase 1 (RACK1) is an evolutionarily conserved scaffold protein, its functional role and mechanistic involvement in PDA pathogenesis remain elusive.</p><p><strong>Methods: </strong>Using multimodal approaches including: (1) genetically engineered mouse models of pancreatitis and carcinogenesis, (2) patient-derived PDA tissues with matched normal specimens, (3) primary acinar cell 3D cultures, and (4) orthogonal gain/loss-of-function assays in PDA cell lines, we systematically investigated RACK1's spatiotemporal expression patterns and functional impacts. Mechanistic dissection was performed through gene expression profiling and pathway enrichment analyses with functional validation.</p><p><strong>Results: </strong>RACK1 exhibited progressive silencing across pancreatic lesion progression: acinar cells (normal) > ADM > pancreatic intraepithelial neoplasia (PanIN) > PDA. This acinar-specific protein was undetectable in ductal/islet lineages and was further suppressed under inflammatory challenge. Functionally, RACK1 depletion accelerated ADM initiation and enhanced PDA cell motility and metastatic dissemination in vivo, whereas its overexpression exerted tumor-suppressive effects. Mechanistically, caerulein/TGF-α stimulation and Kras^G12D activation converged to inhibit RACK1 while activating MAP2K3-SRC-RELA(p65) signaling nodes, establishing a pro-inflammatory feedforward loop.</p><p><strong>Conclusions: </strong>RACK1 serves as a gatekeeper restraining inflammation-driven ADM transformation, with its downregulation constituting an early molecular event in PDA pathogenesis. The RACK1-MAP2K3 axis orchestrates malignant transition through simultaneous NF-κB activation (inflammatory priming) and MAPK hyperactivation (proliferative drive). Our findings nominate RACK1 as both a stratification biomarker for high-risk pancreatic lesions and a druggable node for intercepting preneoplastic progression.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.","authors":"Tali S Skipper, Kristie-Ann Dickson, Christopher E Denes, Matthew A Waller, Tian Y Du, G Gregory Neely, Nikola A Bowden, Alen Faiz, Deborah J Marsh","doi":"10.1007/s13402-025-01102-4","DOIUrl":"https://doi.org/10.1007/s13402-025-01102-4","url":null,"abstract":"<p><p>Understanding genetic dependencies in cancer is key to identifying novel actionable drug targets to advance precision medicine. Whole-genome CRISPR-knockout library screening methods have facilitated this goal. Pooled libraries of single guide RNAs (sgRNAs) targeting over 90% of the annotated protein coding genome are used to induce gene knockouts in pre-clinical cancer models. Novel genes of interest are identified by evaluating sgRNA dropout or enrichment following selection pressure application. This method is particularly beneficial for researching cancers where effective treatment strategies are limited. One example of a commonly chemoresistant cancer, particularly at relapse, is the low survival malignancy epithelial ovarian cancer (EOC), made up of multiple histotypes with distinct molecular profiles. CRISPR-knockout library screens in pre-clinical EOC models have demonstrated the ability to predict biomarkers of treatment response, identify targets synergistic with standard-of-care chemotherapy, and determine novel actionable targets which are synthetic lethal with cancer-associated mutations. Robust experimental design of CRISPR-knockout library screens, including the selection of strong pre-clinical cell line models, allows for meaningful conclusions to be made. We discuss essential design criteria for the use of CRISPR-knockout library screens to discover genetic dependencies in cancer and draw attention to discoveries with translational potential for EOC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of neoadjuvant targeted therapy on the tumor microenvironment in resectable lung adenocarcinoma.","authors":"Ling Yi, Heng Yao, Zhexin Bai, Ziwei Xu, Huimin Li, Yuting Cheng, Chong Wang","doi":"10.1007/s13402-025-01101-5","DOIUrl":"https://doi.org/10.1007/s13402-025-01101-5","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant targeted therapy has emerged as a promising strategy for resectable non-small cell lung cancer (NSCLC). The analysis of the immune status of tumor microenvironment (TME) after targeted therapies is crucial for understanding the impact of targeted therapy on the TME and providing a basis for synergistic therapeutic approaches.</p><p><strong>Methods: </strong>Forty-two patients with resectable lung adenocarcinoma (LUAD) were enrolled in this study, and multiplex immunofluorescence technology was used to explore the immune status of the TME after neoadjuvant targeted therapies.</p><p><strong>Results: </strong>Among the 42 patients, 9 (21.4%) and 33 (78.6%) had ALK and EGFR mutations, respectively, and TKIs were their first-line treatment. All patients received R0 resection, and thoracoscopic minimally invasive surgery were the predominant method. Seven (16.7%) patients reached pathological complete response (pCR), 4 (9.5%) get major pathological response (MPR), and these 11 patients were classified into the MPR group. The remaining 31 (73.8%) patients were non-MPR. The densities of CD8 + T cells (P < 0.001, P = 0.001), GZMB + CD8 + T cells (P = 0.004, P = 0.008), PD-1 + CD8 + T cells (P = 0.019, P = 0.036), macrophages (P = 0.020, P = 0.007), M1 macrophages (P = 0.010, P = 0.007), and ratios of CD8 + T/Treg (P < 0.001, P = 0.026) in TME were significantly higher in the MPR group and ALK mutation group compared with non-MPR and EGFR group. There were positive correlations between CD8 + T cells, PD-1 + CD8 + T cells (r = 0.397, P = 0.009) and GZMB + CD8 + T cells (r = 0.351, P = 0.023); CD8 + T cells and macrophages (r = 0.343, P = 0.026), and M1 macrophages (r = 0.412, P = 0.007). Additionally, eleven patients experienced disease progress during the follow-up period, and the Log-Rank test revealed that MPR patients tended to get longer PFS compared with non-MPR patients (P = 0.063), especially patients with higher densities of macrophages in the TME had significantly longer PFS (P = 0.042).</p><p><strong>Conclusion: </strong>TKI-targeted therapy could reduce tumor burden, facilitating complete surgical resection. Patients with MPR and ALK mutations had a higher density of inflammatory immune cells in the TME and those with higher densities of macrophage had significantly longer PFS.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of microbiota in lung cancer: a new perspective on lung cancer development and treatment.","authors":"Chenxi Yan, Yanjie Chen, Yitao Tian, Shaojie Hu, Heng Wang, Xiaoxue Zhang, Qian Chu, Shanshan Huang, Wei Sun","doi":"10.1007/s13402-025-01103-3","DOIUrl":"https://doi.org/10.1007/s13402-025-01103-3","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related mortality worldwide, with limited treatment efficacy and frequent resistance to conventional therapies. Recent advances have uncovered the critical influence of the human microbiota-complex communities of bacteria, viruses, fungi, and other microorganisms-on lung cancer pathogenesis and therapeutic responses. This review synthesizes current knowledge on the compositional and functional roles of microbiota across multiple body sites, including the gut, lung, tumor microenvironment, circulation, and oral cavity, highlighting their contributions to tumor initiation, progression, metastasis, and immune regulation. We emphasize the bidirectional communication between microbial metabolites and host immune pathways, particularly the gut-lung axis, which modulates systemic and local antitumor immunity. Importantly, microbiota composition has been linked to differential responses and toxicities in chemotherapy, radiotherapy, targeted therapy, and immune checkpoint blockade. Microbiota-targeted interventions, such as probiotics, fecal microbiota transplantation, and selective antibiotics, show promising potential to enhance treatment efficacy and mitigate adverse effects. However, challenges remain in clinical translation due to interindividual microbiome variability, mechanistic complexities, and limited longitudinal data. Future research integrating multi-omics, microbial functional profiling, and controlled clinical trials is essential to harness the microbiome as a precision medicine tool in lung cancer management. This review provides a comprehensive overview of the emerging role of microbiota in lung cancer development and therapy, offering new perspectives for innovative therapeutic strategies.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating multi-modal transcriptomics identifies cellular subtypes with distinct roles in PDAC progression.","authors":"Jun Wu, Tenghui Dai, Ziyue Li, Meng Pan, Wei Zhang, Hao Chen, Guansheng Zheng, Li Qiao, Qizhou Lian, Yang Liu, Jierong Chen","doi":"10.1007/s13402-025-01100-6","DOIUrl":"https://doi.org/10.1007/s13402-025-01100-6","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, largely due to its highly immunosuppressive and fibrotic tumor microenvironment (TME). However, the spatial and functional organization of its cellular components remains poorly understood.</p><p><strong>Methods: </strong>We present an integrated transcriptomic atlas of the PDAC TME by combining single-cell RNA sequencing (n = 88; 187,520 cells), Visium spatial transcriptomics (n = 20; 67,933 spots), bulk RNA sequencing (n = 1,383), and high-resolution Xenium spatial transcriptomics (n = 2; 307,679 cells). Key findings were validated using scRNA-seq, bulk datasets, multiplex immunohistochemistry, and spatial imaging.</p><p><strong>Results: </strong>POSTN⁺ fibroblasts and SPP1⁺ macrophages consistently co-infiltrated across 12 independent bulk RNA-seq cohorts, and showed spatial correlation in both Visium and Xenium platforms. Those tumor-promoting cell states were enriched in hypoxic, angiogenesis, and epithelial-mesenchymal transition, and were linked to poor prognosis. In contrast, CCL4⁺ CD8⁺ effector T cells and IGHG1⁺ plasma cells co-occurred within immune-active niches, were enriched for cytotoxic and activation-related pathways, and were associated with improved patient survival. Notably, these protective immune subsets remained detectable despite the immunosuppressive nature of the PDAC TME. Expression specificity of POSTN, SPP1, CCL4, and IGHG1 was validated at the transcriptomic and protein levels.</p><p><strong>Conclusions: </strong>We delineate two opposing cellular programs in the PDAC TME-tumor-promoting stromal remodeling and anti-tumor immune activation-spatially organized in distinct niches. Those findings suggest that targeting POSTN⁺ fibroblasts and SPP1⁺ macrophages-mediated stromal interactions while promoting CCL4⁺ T cell and IGHG1⁺ plasma cell immunity, may offer new therapeutic strategies for PDAC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular stratification of prostate cancer through sensory perception-related multi-omics analysis reveals chemoresistant mechanisms.","authors":"Shi Li, Ye Tian, Yu Sun, Tian Xu, Wei Wang","doi":"10.1007/s13402-025-01099-w","DOIUrl":"10.1007/s13402-025-01099-w","url":null,"abstract":"<p><strong>Background: </strong>Advanced prostate cancer (PCa) displays significant genetic heterogeneity and therapy resistance, yet the role of sensory perception pathways in its progression remains unclear.</p><p><strong>Methods: </strong>We performed an integrative multi-omics analysis of sensory perception-linked mRNAs and lncRNAs from TCGA and scRNA-seq data. Unsupervised consensus clustering defined three molecular subtypes (CS1-CS3). Key biomarkers were validated in patient tissues and serum. Immune and stromal infiltration were quantified using TIDE and ESTIMATE. Single-cell trajectories characterized TSC22D3-positive T cells, and NicheNet mapped ligand-receptor interactions.</p><p><strong>Results: </strong>Three subtypes emerged, with CS1 showing the poorest prognosis, marked chemotherapy resistance, and pronounced stromal-immune crosstalk. CS1 tumors exhibited elevated B- and T-cell infiltration and increased oxidative phosphorylation in TSC22D3-positive T cells. NicheNet analysis identified the TNF-CCL20 axis as a central mediator of immunosuppressive signaling and chemoresistance in CS1.</p><p><strong>Conclusions: </strong>This study establishes sensory perception-associated molecular subtypes in PCa and links CS1 chemoresistance to immune microenvironment reprogramming via TNF-CCL20 signaling. These findings offer mechanistic insights into PCa progression and suggest actionable targets to overcome therapeutic resistance.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL1-WDR4 promotes the migration and proliferation of gastric cancer through N⁷-methylguanosine.","authors":"Jiaqi Wang, Kai Zhou, Tao He, Qihang Hu, Jianquan Liu, Pingang Li, Yan Shi, Jun Song, Peiwu Yu","doi":"10.1007/s13402-025-01094-1","DOIUrl":"https://doi.org/10.1007/s13402-025-01094-1","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common malignant tumor worldwide. Metastasis is leading cases of cancer-related death of GC. It has been found that N⁷-methylguanosine (m7G) modifications play an important role in cancer. However, the role of m7G modifications within mRNA and its \"writer\" METTL1 and WDR4 in tumors, particularly GC, has not been revealed.</p><p><strong>Methods: </strong>RT-qPCR, WB and IHC were used to detect the expression of METTL1 and WDR4 in GC cells and tissues. Function-based experiments were performed using METTL1-WDR4 knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and nude mice models. Mechanistically, RNA-seq, MeRIP-seq, MeRIP-qPCR, western blot, dot blot, co-IP, ChIP and IHC stainings were performed.</p><p><strong>Results: </strong>METTL1 and WDR4 were upregulated in GC patients. High expression of METTL1 and WDR4 were associated with poor prognosis. Silencing METTL1-WDR4 inhibited GC cell migration and proliferation in vitro and vivo. Mechanistically, METTL1-WDR4 can enhance the mRNA stability of PIK3C2B and AKT by promoting their m7G levels, which leading the overexpression of p-AKT. Interestingly, we also found that on the one hand, the transcription factor YY1 can promote the mRNA transcription expression of METTL1 and WDR4 at the same time, and on the other hand, METTL1-WDR4 can promote YY1 expression by increasing the level of m7G. This regulation presents positive feedback. Above all, METTL1 and WDR4 ultimately up-regulate the level of m7G and promote the malignant progression of GC.</p><p><strong>Conclusions: </strong>These findings suggest that METTL1-WDR4 might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for GC treatment by regulating m7G level.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors.","authors":"Yanan Yu, Chengjiang Wei, Minghui Yue, Cheng Zhang, Yixiao Wang, Zhichao Wang","doi":"10.1007/s13402-025-01054-9","DOIUrl":"10.1007/s13402-025-01054-9","url":null,"abstract":"<p><p>Almost all patients of Neurofibromatosis Type I (NF1) develop benign peripheral nerve tumors called neurofibromas, which are derived from neural crest Schwann cell lineage progenitors with biallelic NF1 gene mutations. More than 90% of NF1 patients develop dermal neurofibromas (DN), and 25-50% develop plexiform neurofibromas (PN). In 8-13% of individuals with NF1, PN can transform into malignant peripheral nerve sheath tumors (MPNSTs), a type of nerve soft tissue sarcoma that is the main cause of mortality of NF1 patients. In addition to arising from benign neurofibromas (50%), MPNSTs can also occur spontaneously (~40%) or following radiation therapy (~10%). Treatment for MPNST is limited to complete resection with negative margins. Still, the high recurrence of MPNST is a major concern. However, full resection of the pre-malignant lesions can largely reduce the recurrence and mortality of patients. So, early diagnosis and distinguishing malignancy from benign and premalignant lesions are particularly important. During the progression from benign neurofibromas to malignancy, a variety of changes including tumor morphology, genetic mutations, expression of multiple signaling pathways-related proteins and genome instability gradually occur. In this review, we detail these changes with the goals of identifying the histological and/or molecular signs of malignancy initiation, and an optimal therapeutic intervention window, to inhibit tumor progression and reduce the rate of mortality.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"841-857"},"PeriodicalIF":6.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763039","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}