Cellular Oncology最新文献

{"title":"RBM15/IGF2BP2-PTPRH m6A regulatory axis in non-small cell lung cancer.","authors":"Keyue Qiu, Xiaoxiao Zheng, Hongxiang Li, Jiaheng Zhang, Zijun Xie, Hang Chen, Zeyang Hu, Yiyi Sun, Zhe Chen, Jingtao Tong, Yinyu Mu, Yuanyuan Yao, Wei Chen, Guodong Xu","doi":"10.1007/s13402-026-01217-2","DOIUrl":"10.1007/s13402-026-01217-2","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related death globally, highlighting the urgent need for new molecular drivers and therapeutic targets. This study investigates the role of protein tyrosine phosphatase receptor type H (PTPRH) and its regulation through an epitranscriptomic mechanism in NSCLC.</p><p><strong>Methods: </strong>We performed an integrated analysis of datasets from The Cancer Genome Atlas and Gene Expression Omnibus to evaluate PTPRH expression and its prognostic significance. PTPRH levels were further validated in clinical NSCLC specimens and correlated with clinicopathological features. We assessed the functional consequences of PTPRH expression on proliferation, apoptosis, migration, invasion, and angiogenesis using in vitro and in vivo models. The underlying mechanism involving N6-methyladenosine (m6A) modification was explored by examining the roles of the m6A writer RBM15 and the reader IGF2BP2 on PTPRH transcript stability. Gain- and loss-of-function experiments, coupled with rescue studies, were conducted to delineate the functional axis.</p><p><strong>Results: </strong>PTPRH was significantly overexpressed in NSCLC tissues, and its elevated expression correlated with poor patient prognosis. Functionally, PTPRH promoted tumor cell proliferation, migration, invasion, and xenograft tumor growth, while simultaneously inhibiting apoptosis and enhancing angiogenesis via the VEGF pathway. Mechanistically, PTPRH expression was post-transcriptionally stabilized by m6A methylation. RBM15 facilitated m6A deposition on PTPRH transcripts, while IGF2BP2 binding to these modified sites enhanced PTPRH mRNA stability. Depletion of RBM15 or IGF2BP2 reduced PTPRH levels and suppressed malignant behaviors, whereas their overexpression produced the opposite effects. The oncogenic functions of PTPRH were confirmed to be dependent on this regulatory axis.</p><p><strong>Conclusion: </strong>Our study unveils a novel epigenetic regulatory axis in which RBM15-mediated m6A modification and IGF2BP2-dependent recognition stabilize PTPRH mRNA, thereby promoting NSCLC progression. This work expands the understanding of post-transcriptional regulation in lung cancer and identifies the RBM15/IGF2BP2-PTPRH axis as a potential therapeutic target for NSCLC intervention.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866862","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":"Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.","authors":"Vilte Stonyte, Christina Saeten Fjeldbo, Mélanie Langiu, Michelle Joy-Immediato, Priyanka Swaminathan, Prabin Sharma Humagain, Laura Marian Valencia-Pesqueira, Lilian Lindbergsengen, Coen Campsteijn, Heidi Lyng, Beata Grallert","doi":"10.1007/s13402-026-01214-5","DOIUrl":"10.1007/s13402-026-01214-5","url":null,"abstract":"<p><strong>Purpose: </strong>High expression of the stress-response kinase GCN2 has been linked to poor survival in several cancers including cervical cancer, but its underlying biological roles remain incompletely understood. This study aimed to identify genes whose expression correlates with GCN2 in locally advanced cervical cancer and to use these associations to elucidate cellular functions that could contribute to aggressive disease behavior.</p><p><strong>Methods: </strong>Correlation analyses were performed between GCN2 expression and genome-wide mRNA profiles in a biobank of 291 patients with locally advanced cervical cancer. Gene ontology and pathway analyses were used to identify enriched biological processes, and functional assays were conducted to validate GCN2 involvement in selected pathways.</p><p><strong>Results: </strong>GCN2 expression correlated not only with genes involved in cellular stress responses but also with those regulating mitosis and cell migration. Functional analyses confirmed that GCN2 activity promotes both proliferative and migratory capacities, revealing important cancer-relevant roles beyond its canonical function in translational control.</p><p><strong>Conclusion: </strong>Our findings demonstrate that elevated GCN2 levels support cellular functions that can contribute to tumor aggressiveness. These results suggest that GCN2 plays a direct role in malignant progression and may represent a potential biomarker or therapeutic target in locally advanced cervical cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866906","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":"Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons.","authors":"Yanyun Hong, Xiaodong Wang, Hang Yu, Xiaosun Liu, Chao Tang","doi":"10.1007/s13402-026-01218-1","DOIUrl":"10.1007/s13402-026-01218-1","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a leading cause of cancer-related mortality globally and is characterized by significant inter- and intra-tumoral heterogeneity, which poses major challenges to effective treatment. Although traditional \"one-size-fits-all\" chemotherapy regimens have improved outcomes, the prognosis for advanced disease remains poor, necessitating a paradigm shift towards personalized medicine. This review provides a comprehensive synthesis of the current landscape of precision oncology in GC. We systematically analyze the clinical implications of major molecular classification systems, particularly The Cancer Genome Atlas (TCGA) subtypes (EBV-positive, MSI-H, GS, and CIN), and their role in guiding therapeutic stratification. The integration of molecular profiling has revolutionized the management of GC. We discuss the evolution of targeted therapies, ranging from established standards, like HER2 inhibition, to emerging targets, including Claudin18.2 and FGFR2, highlighting their potential of overcoming resistance mechanisms. Furthermore, we evaluate the efficacy of immune checkpoint inhibitors (PD-1/PD-L1 blockade), specifically in the context of high microsatellite instability (MSI-H) and EBV-positive subtypes, where these have demonstrated robust antitumor activity. Beyond tissue-based markers, this article also explores the expanding role of liquid biopsies, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), as non-invasive tools for real-time monitoring of disease progression and therapeutic response. Precision oncology represents a transformative approach in GC, moving beyond histology to a molecularly driven treatment framework. However, realizing its full potential requires addressing challenges related to tumor heterogeneity and drug resistance. Future research must focus on validating novel biomarkers and developing synergistic combination strategies to further improve patient survival.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863562","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":"Integrative analysis and functional validation identified palmitoylated PHGDH as a therapeutic target for colon adenocarcinoma.","authors":"Yixian Song, Lingling Lin, Dejian Liu, Mengqing Zhu, Pei Wang, Ke Li, Aimin Li, Kequan Chen, Zhanhui Ye","doi":"10.1007/s13402-026-01207-4","DOIUrl":"10.1007/s13402-026-01207-4","url":null,"abstract":"<p><p>BACKGROUND: Colon adenocarcinoma (COAD) has high incidence and mortality with poor prognosis, creating an urgent need for novel prognostic models and therapeutic strategies. Protein palmitoylation, an important post-translational modification, exerts pivotal effects on tumorigenesis; however, its prognostic and mechanistic relevance in COAD remains unknown. This study determined palmitoylation-related prognostic biomarkers and probable therapeutic targets to treat COAD. METHODS: We integrated transcriptomic datasets from the TCGA and identified prognostic genes related to palmitoylation by conducting differential expression analysis, weighted gene correlation network analysis, and Cox proportional hazards modeling using the least absolute shrinkage and selection operator (LASSO) method. Based on these genes, we established a robust risk signature and nomogram that consistently stratified COAD patients into distinct risk groups. Multi-omics profiling, including immune infiltration assessment, drug response prediction, and single-cell mapping, revealed distinct molecular and cellular programs within each risk group. In vitro and in vivo studies were conducted using the representative hub gene PHGDH to validate its function in COAD. RESULTS: A risk score model comprising three palmitoylation-related genes (PHGDH, LAMA2, and PBXIP1) stratified COAD patients into subgroups with distinct survival, immune infiltration, and drug sensitivity profiles. PHGDH was identified as the most dysregulated candidate. Functional studies revealed that depleting PHGDH significantly repressed cell proliferation and induced apoptosis. Critically, pharmacological inhibition of PHGDH palmitoylation markedly suppressed tumor growth in vitro and in xenograft models, indicating its feasibility as a therapeutic target for COAD. CONCLUSION: The palmitoylation-related risk model established in this study demonstrates strong prognostic predictive capability for COAD, offering a promising new clinical stratification tool. Furthermore, PHGDH was validated as a key functional target whose activity is regulated by palmitoylation, presenting a novel therapeutic opportunity for COAD treatment. </p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670692","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":"BCAA catabolism mediates POU2AF1 propionylation to enhance T-ALL development.","authors":"Sijia Dan, Yilu Xu, Li Xie, Xiaoxiao He, Haotian Liu, Lu Zhao, Liyuan Cao, Bo Qu, Yan Lu, Chiqi Chen, Zhuo Yu, Jiangbo Wan, Pu Chen, Junke Zheng","doi":"10.1007/s13402-026-01201-w","DOIUrl":"10.1007/s13402-026-01201-w","url":null,"abstract":"<p><p>PURPOSE: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive, life-threatening hematological malignancy with limited therapeutic regimens. While metabolic reprogramming is known to play critical roles in leukemogenesis, how distinct metabolic pathways orchestrate T-ALL pathogenesis remains largely unknown. We herein aim to unravel how the branched-chain amino acid (BCAA) metabolism fine-tunes T-ALL cell fates. METHODS: Metabolomic and transcriptomic analyses were performed to identify branched-chain amino acid transaminase 1 (BCAT1)-associated metabolic and molecular alterations. Functional studies in murine T-ALL models were conducted to evaluate the role of BCAT1 in leukemia development, including the assessment of leukemia burden by flow cytometry during T-ALL development. Biochemical and molecular assays were used to assess POU2AF1 propionylation and its downstream signaling. Clinical datasets were analyzed to investigate the clinical relevance of BCAT1 in T-ALL. RESULTS: We revealed that BCAT1 could serve as a critical driver to sustain T-ALL initiation and progression. BCAT1 was highly expressed in both murine and human T-ALL cells and was critical for the self-renewal and homing capacities of leukemia cells. Mechanistically, BCAT1-mediated BCAA catabolism promoted the propionylation of transcriptional coactivator POU2AF1, which further enhanced its ability to transactivate SLC7A11 expression to suppress ferroptosis and support the proliferation of T-ALL cells. Moreover, BCAT1 expression levels were strongly correlated with poor prognosis in T-ALL patients. Combined treatment with dietary BCAA restriction and immune checkpoint blockade synergistically inhibited T-ALL progression. CONCLUSION: Our findings reveal a novel mechanism whereby BCAA catabolism mediates ferroptosis resistance through POU2AF1 propionylation during T-ALL progression. Therapeutic blockade of the BCAT1-POU2AF1-SLC7A11 axis holds considerable translational potential in T-ALL treatment. </p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670724","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":"Bacterial taxa associated with lung cancer cases in Southeast Asians: a pilot case-control study.","authors":"Adrian Low, Yah Ru Juang, Fransiskus X Ivan, Lina Ang, Luke Hao Shuan Ooi, Sean Wei Jun Chan, Micheal Mac Aogain, Tavleen Kaur Jaggi, Sanjay H Chotirmall, Yann Felix Boucher, Anthony Chau Ang Yii, Mariko Siyue Koh, Darren Wan Teck Lim, Jonathan Wei Jie Lee, Wei Jie Seow","doi":"10.1007/s13402-026-01193-7","DOIUrl":"10.1007/s13402-026-01193-7","url":null,"abstract":"<p><p>PURPOSE: Lung cancer is the leading cause of cancer-related mortality worldwide, yet its underlying mechanisms remain unclear. Disruptions in the respiratory microbiome may promote inflammation and carcinogenesis. This study aimed to comprehensively compare genus-level sputum microbiota between lung cancer patients and healthy controls in a multiethnic Southeast Asian population. METHODS: Sputum samples were collected from lung cancer patients across three Singapore hospitals. Socio-demographic data were obtained via questionnaire. We analyzed 16S rRNA amplicon sequences from 70 lung cancer patients and 47 healthy controls from a separate local cohort, using identical sequencing protocols to minimize batch effects. Alpha- and beta-diversity metrics, random forest models, and ANCOM-BC2 were used to identify microbial features associated with lung cancer and host characteristics. RESULTS: Lung cancer cases showed significantly reduced genus richness compared to controls. Beta-diversity (Aitchison distance) differed by case-control status, sex, age, and smoking history. ANCOM-BC2 identified Lactobacillus as differentially enriched in cases. However, this enrichment did not pass the pseudo-count test among never-smokers. Further sex-stratified analysis revealed that the Lactobacillus enrichment was driven primarily by male cases. Conversely, [Eubacterium] nodatum group, Mogibacterium, and Campylobacter emerged as robust inverse signatures for lung cancer, with their depletion consistently supported across stratified and unstratified differential abundance analyses, random forest modeling, and Wilcoxon rank-sum tests. However, these findings may still be subjected to residual confounding by exogenous factors, such as medication use, which could not be adequately adjusted for between case-control groups. CONCLUSION: This pilot case-control study, conducted in a multiethnic Southeast Asian population, identified distinct respiratory microbiota signatures associated with lung cancer using robust differential abundance and machine-learning methods, providing preliminary evidence for a potential role of the respiratory microbiome to lung carcinogenesis, warranting validation in larger, longitudinal studies. </p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644023","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":"A habitat radiomics model based on contrast-enhanced MRI for predicting early treatment response to hepatic arterial infusion chemotherapy in patients with unresectable hepatocellular carcinoma.","authors":"Guanhui Li, Xuefei Zhao, Jie Long, Yi Li, Zhexuan Ye, Lili Rao, Yuqin He, Shujie Lai, Yuxin Tang, Hao Zhong, Chao Li, Jie Li, Changxu Cai, Hao Wu, Xiang Lan, Nan You, Jun Wang, Liangzhi Wen","doi":"10.1007/s13402-026-01196-4","DOIUrl":"10.1007/s13402-026-01196-4","url":null,"abstract":"<p><p>PURPOSE: To develop a contrast-enhanced Magnetic Resonance Imaging (CEMRI)-based habitat radiomics model for predicting early treatment response to hepatic artery infusion chemotherapy with fluorouracil, leucovorin, and oxaliplatin (HAIC-FOLFOX) in patients with unresectable hepatocellular carcinoma (HCC) and elucidate the underlying biological mechanisms. METHODS: Among 120 HCC patients who underwent HAIC treatment, habitat features were extracted by applying clustering algorithms to preoperative CEMRI to delineate intratumoral subregions with distinct enhancement characteristics. Least absolute shrinkage and selection operator (LASSO) and logistic regression were employed for feature selection to construct habitat, conventional radiomics, clinical, and combined models. Internal validation was performed using 1000 bootstrap resamples. In a separate cohort of 107 surgically resected HCC patients, the habitat model was applied for risk stratification, and correlations between habitat features and pathomorphological characteristics, as well as immunohistochemical (IHC) markers, were investigated. RESULTS: MRI images were categorized into three distinct habitats, and a predictive model was built from their proportional distribution. The habitat radiomics model achieved an area under the curve (AUC) of 0.868 (95% confidence interval (CI): 0.748–0.976), outperforming both conventional radiomics (AUC 0.849, 95% CI: 0.719–0.954) and clinical models (AUC 0.653, 95% CI: 0.497–0.802). The combined clinical-habitat model reached the highest AUC of 0.901 (95% CI: 0.795–0.989, P < 0.05). In the surgical cohort, low-risk habitat patients exhibited increased tumor necrosis/stromal components (elevated IntensityMin) and better differentiation (reduced CurvMean) (P < 0.05). Immunohistochemistry revealed higher microvessel density (CD34) and lower cancer stem cell marker expression (CK19, Glypican-3) in the low-risk group (P < 0.05). CONCLUSION: The CEMRI habitat radiomics model accurately predicts early HAIC treatment response, with risk stratification significantly correlated with pathomorphological and molecular characteristics. </p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503308","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":"Targeting senescence-like tumor-associated macrophages sensitizes chemotherapy in triple-negative breast cancer.","authors":"Hongxu Zhou, Chengzhao Xu, Jiabeini Zhang, Yangxuzhu Liu, Xiaochuan Gao, Ziqi He, Yuheng Wu, Qian Zhao, Baoling Liang, Dong Song","doi":"10.1007/s13402-026-01197-3","DOIUrl":"10.1007/s13402-026-01197-3","url":null,"abstract":"<p><p>PURPOSE: Triple-negative breast cancer (TNBC) frequently develops chemoresistance through poorly understood stromal interactions. This study aimed to elucidate the mediating role of chemotherapy-induced senescence-like tumor-associated macrophages (TAMs) in this process, including the underlying mechanisms and therapeutic potential. METHODS: Orthotopic TNBC models were employed to investigate doxorubicin (Adriamycin, ADM))-induced senescence-like phenotypes in TAMs. The senolytic agent ABT263 combined with IL-6 signaling blockade was administered in vivo to evaluate the restoration of chemosensitivity. Additionally, multiplexed immunofluorescence analysis was conducted on clinical TNBC specimens to assess the correlation between TAMs exhibiting senescence-like phenotypes and clinical outcomes. RESULTS: ADM chemotherapy induces a TAM senescence-like phenotype, marked by p16/p21 upregulation and acquisition of a senescence-associated secretory phenotype. Senescence-like TAMs exhibited pronounced IL-6 secretion, which activated the IL-6R/STAT3 axis in TNBC cells to drive the expression of drug-resistance genes and stemness markers. Depletion of senescence-like cells with the senolytic agent ABT263 or blockade of IL-6 signaling restored chemosensitivity in vivo, substantially enhancing ADM efficacy. Crucially, multiplexed immunofluorescence of clinical TNBC specimens revealed that senescence-like TAMs accumulate in chemotherapy-treated tumors and correlate with progressive disease (PD) rather than the therapeutic response (CR/PR). CONCLUSION: This study identifies chemotherapy-induced senescence-like TAMs as a key druggable driver of TNBC chemoresistance and highlights senolysis and IL-6 inhibition as strategies to overcome therapeutic resistance. </p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503399","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":"CX3CL1-CX3CR1 signaling orchestrates malignant progression of prostate cancer through luminal progenitor-macrophage crosstalk.","authors":"Yu Jiang, Yuchen Guo, Lizhuang Han, Shiwei Wang, Fang Wang, Yongliang Zhao, Jiajia Wang, Junyan Han, Miaomiao Liu, Zhihua Liu, Qin Zhang","doi":"10.1007/s13402-026-01179-5","DOIUrl":"10.1007/s13402-026-01179-5","url":null,"abstract":"<p><strong>Purpose: </strong>Progression to castration-resistant prostate cancer (CRPC) is shaped by dynamic interactions within the tumor microenvironment (TME). However, the specific cellular crosstalk driving therapeutic resistance and metastasis remains incompletely defined. This study aims to identify key signaling axes between therapy-resistant luminal progenitor (luminal-2) cells and immune components in the TME, particularly tumor-associated macrophages (TAMs), and to determine how these interactions promote immunosuppression and cancer stem-like cell expansion during disease progression.</p><p><strong>Methods: </strong>We employed an integrative phenomics approach combining single-cell transcriptomics with genetically engineered mouse models (GEMMs) and orthotopic allograft models of prostate cancer. Spatiotemporal changes in cell populations were profiled across disease stages. The functional contribution of the CX3CL1-CX3CR1 axis was evaluated through genetic ablation of Cx3cr1 in host mice, followed by assessment of TAM infiltration, luminal progenitor cell dynamics, tumor growth, and immunosuppression signature score.</p><p><strong>Results: </strong>Single-cell profiling revealed a distinct luminal-2 progenitor population with high CX3CL1 expression that recruits CX3CR1⁺ TAMs and supports a pro-tumoral program. These CX3CL1^hi luminal-2 cells and CX3CR1^hi TAMs expand in a stage-specific manner and co-evolve during CRPC progression, forming an immunosuppressive and pro-metastatic niche. Host Cx3cr1 deletion disrupted this signaling axis, leading to reduced TAM infiltration, suppression of luminal progenitor cells expansion, and significant inhibition of tumor growth and progression.</p><p><strong>Conclusion: </strong>The CX3CL1-CX3CR1 axis functions as a critical mediator of reciprocal signaling between luminal-2 progenitors and TAMs that promotes immune evasion, stemness maintenance, and therapeutic resistance in prostate cancer. Disrupting this pathway impairs the pro-tumoral niche and may represent a promising therapeutic approach for advanced prostate cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503299","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":"Targeting sialic acid metabolism: a therapeutic strategy against gastric cancer driven by WZ35.","authors":"Boxiang Hong, Ying Wang, Xinran Feng, Lihan Wei, Yichen Huang, Xiawei Zhang, Longyuchen Xu, Pinyan Jin, Liyuan Huang, Rui Li, Xinyu Wu, Zhi Li, Hangyu Ye, Tongke Chen, Xiaoyan Wang, Hao Zhang","doi":"10.1007/s13402-026-01194-6","DOIUrl":"10.1007/s13402-026-01194-6","url":null,"abstract":"<p><p>Glycolytic reprogramming is closely associated with the occurrence and progression of gastric cancer. Specifically, the energy derived from glucose metabolism and the cellular proteins by its intermediate products influence gastric cancer development. However, as an important branch of glucose metabolism, sialic acid metabolism and its mediated sialylation modifications remain insufficiently studied in gastric cancer, and their specific relationship with malignant tumor progression requires further exploration. This study employed a multi‑omics approach, integrating metabolomics, single‑cell RNA sequencing, and bulk RNA sequencing analyses, to investigate the metabolic landscape of gastric cancer and its associated alterations. The results indicated that sialic acid is a characteristic metabolite in malignant gastric cancer tissues. It modulates biological functions such as immune response, proliferative activity, and metabolic remodeling within gastric cancer tissues by influencing sialylation modifications. Furthermore, we identified the drug WZ35, which can inhibit the malignant proliferation of gastric cancer by targeting both sialic acid metabolism and sialylated protein modifications. We put forward a conjecture that the metabolism and modification of sialic acid promote the malignant development of gastric cancer, and we discovered that the drug WZ35 has an inhibitory effect on the sialic acid metabolism of gastric cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503355","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}