Cellular Oncology最新文献

{"title":"Enriched environment inhibits melanoma by reshaping gut microbiota and enriching Parabacteroides distasonis.","authors":"Xin Li, Huimin Li, Qing Wang, Xiang Gao, Jian Gao, Min Du, Wei Zhang, Shunan Liu, Yiyi Liang, Qian Li, Yu Gan, Hong Tu","doi":"10.1007/s13402-026-01249-8","DOIUrl":"10.1007/s13402-026-01249-8","url":null,"abstract":"<p><strong>Purpose: </strong>The role of psychological factors in the holistic regulation of cancer has garnered significant attention. Psychological eustress induced by an enriched environment (EE) inhibits various cancers including melanoma, but underlying mechanisms remain largely unknown. The brain-gut axis may play a key role in modulating psychological factors and cancer progression. This study investigates the role of gut microbiota in EE-induced anti-melanoma effects.</p><p><strong>Methods: </strong>C57BL/6 mice were housed in EE or standard environment (SE). Longitudinal fecal samples from EE and SE mice underwent 16S rRNA gene sequencing. SE melanoma-bearing mice received fecal microbiota transplantation (FMT) from EE or SE donors to assess the microbiota's causal role in EE's anti-tumor effects. Bacterial species upregulated by EE in tumor-bearing mice were identified;Parabacteroides distasonis (Pd) was selected for therapeutic administration. Immune cells in spleen and tumor were quantified by flow cytometry. Natural killer (NK) cell function was tested using anti-NK1.1 depletion.</p><p><strong>Results: </strong>EE increased the alpha diversity of the gut microbiota and alleviated the dysbiosis caused by melanoma. FMT from EE mice to SE mice inhibited melanoma growth, suggesting that the gut microbiota contributes to EE's anti-tumor effects. EE upregulated seven bacterial species in tumor-bearing mice, including Pd. Oral administration of Pd inhibited melanoma growth and increased intratumoral NK/NKT cell proportions and NK cell granzyme B expression. NK cell depletion abrogated Pd's anti-tumor effect.</p><p><strong>Conclusion: </strong>This study underscores the interconnectedness of psychological eustress, gut microbiota, and cancer, providing preclinical insights into holistic cancer treatments. Leveraging the brain-gut-cancer axis, targeting psychological factors and gut microbiota could offer a potential adjunctive strategy for melanoma management.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374619","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":"Neural regulation of cancer: from synaptic integration to neuro-immune regulation.","authors":"Xiaomeng Li, Yuxin Li, Xiaoyan Shi, Yunyun Wang, Shaoping Ji","doi":"10.1007/s13402-026-01250-1","DOIUrl":"10.1007/s13402-026-01250-1","url":null,"abstract":"<p><p>The emerging field of cancer neuroscience has reshaped our understanding of tumor biology, showing that the nervous system is an active participant in the tumor microenvironment. It modulates tumor progression through synaptic communication with cancer cells, paracrine signaling via neurotransmitters and neuropeptides, and indirect regulation of the tumor immune microenvironment. Recent discoveries have shown that neurons form synapses with brain tumors and peripheral cancers, driving tumor cell proliferation and invasion. Neurotransmitter and neuropeptide signaling activates pathways in cancer cells to promote malignancy. Furthermore, the nervous system shapes anti-tumor immunity by modulating T cells, natural killer cells, macrophages, and myeloid-derived suppressor cells, creating either an immunostimulatory or, more commonly, an immunosuppressive microenvironment that facilitates immune evasion and treatment resistance. The clinical significance of the neuro-immune-tumor axis is confirmed across multiple cancer types. Consequently, therapeutic strategies targeting neural regulation are emerging, including neurotransmitter receptor blockers, denervation techniques, neuromodulation devices, and approaches to remodel the immune landscape through neural signals. This review synthesizes how nerves regulate tumor progression via synaptic connections, neurotransmitter release, and immune modulation. We also summarize current and emerging therapeutic strategies aimed at disrupting or harnessing neuro-tumor communication. By integrating recent advances, this review aims to establish a framework for understanding neural regulation of cancer and to guide future research and clinical translation in this evolving field.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374690","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":"Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.","authors":"Yuqi Ding, Xiaoxue Ren, Ye Yang, Peiqi Cai, Shuling Chen, Yubin Xie, Miaoling Tang, Xiaofei Liu, Shaoqing Huang, Yu Yang, Jiale Chen, Wenxuan Xie, Kaiyu Sun, Xinhua Zhang","doi":"10.1007/s13402-026-01247-w","DOIUrl":"10.1007/s13402-026-01247-w","url":null,"abstract":"<p><strong>Purpose: </strong>Gastrointestinal stromal tumors (GISTs), the most common gastrointestinal sarcomas, experience a high rate of resistance to standard treatment tyrosine kinase inhibitor (TKI) imatinib, leading to tumor progression. Identifying non-responders and offering precise alternatives are crucial, however, multi-omics studies of GIST are limited, which hinders GIST biology understanding and novel drug development.</p><p><strong>Methods: </strong>We performed whole-exome and transcriptomic sequencing on 106 primary GIST patients. Subtype-specific molecular features and therapeutic responses were further validated in vitro and in vivo.</p><p><strong>Results: </strong>Unsupervised clustering analysis of RNA data classified them into four subtypes, including immune (G1), stromal (G2), proliferative (G3), and metabolic (G4) subtypes. The G4 subtype had more patients with primary non-gastric tumors, a poor response to neoadjuvant imatinib treatment and synchronous metastasis, with an overall poor prognosis. Notably, G4 subtype exhibited significantly enhanced aerobic metabolism. Moreover, G4 subtype harbored homologous recombination repair deficiency (HRD) signatures, with significantly reduced homologous recombination activity and upregulation of non-homologous repair pathways. By stratifying GIST cell lines into subtypes, we confirmed that the HRD-targeting poly ADP-ribose polymerase (PARP) inhibitor Olaparib suppressed tumor growth in the G4 subtype-representative GIST882 cell line. In vivo experiments demonstrated that Olaparib monotherapy significantly reduced tumor burden in GIST882 xenograft-bearing mice and synergized with imatinib.</p><p><strong>Conclusion: </strong>We systematically deconstructed the molecular subtypes of primary GISTs by integrated genomic and transcriptomic analysis. A specific GIST subtype characterized by poor treatment responses and prognosis, marked by the activation of aerobic metabolism and HRD features, may be a potential candidate for PARP inhibitors.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359619","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":"RRM1 competes with NEDD4 to stabilize USP19 by blocking K387 ubiquitination and suppresses autophagy-mediated chemoresistance in colorectal cancer.","authors":"Lingxiao Wang, Weixing Zhang, Yifan Kang, Yingjia Wang, Shenghuai Hou, Fan Wang, Yuqiao Bai, Ruijun Ma, Jian Yang, Yaoping Li","doi":"10.1007/s13402-026-01245-y","DOIUrl":"10.1007/s13402-026-01245-y","url":null,"abstract":"<p><strong>Background: </strong>Resistance to 5-fluorouracil (5-FU) remains a major clinical challenge in colorectal cancer (CRC) treatment. This study investigates the non-canonical role of ribonucleotide reductase subunit M1 (RRM1) in regulating autophagy-mediated chemoresistance.</p><p><strong>Methods: </strong>A comprehensive multi-omics strategy, including metabolomics, transcriptomics and proteomics analyses, was employed to study 5-fluorouracil-resistant colorectal cancer tissues from patients and matched drug-resistant cell models. Protein-protein interactions, ubiquitination events and functional consequences were validated via complementary assays including Co-IP, GST pull-down, in vivo ubiquitination, structure-guided molecular docking, site-directed mutagenesis, and subcutaneous xenograft mouse models. Structure-based virtual screening was conducted to identify candidate compounds targeting the RRM1-USP19 interaction, with in vivo anti-tumor activity verified in 5-FU-resistant CRC xenografts.</p><p><strong>Results: </strong>RRM1 is significantly downregulated in 5-FU-resistant CRC tissues, and low RRM1 expression correlates with poor clinical prognosis. Mechanistically, RRM1 directly binds USP19 via conserved E647/R648 residues, competitively blocking NEDD4-mediated USP19 K387 ubiquitination and subsequent proteasomal degradation. Loss of RRM1 destabilizes USP19, impairs autophagic substrate deubiquitination, hyperactivates autophagic flux and thereby induces 5-FU resistance. Restoration of RRM1 or expression of the ubiquitination-defective USP19-K387R mutant re-sensitizes resistant CRC cells to 5-FU. The peptide GAGGVGKSAL, identified via virtual screening, specifically disrupts the RRM1-USP19 interface, inhibits excessive autophagy and potently suppresses tumor progression in 5-FU-resistant CRC xenograft models.</p><p><strong>Conclusions: </strong>This study identifies the novel RRM1-USP19-NEDD4 regulatory axis as a core mediator of autophagy-driven 5-FU resistance in CRC, uncovers a non-canonical, metabolism-independent role of RRM1 as a USP19 stabilizer via competitive inhibition of NEDD4-mediated ubiquitination, and validates GAGGVGKSAL as a promising lead compound targeting this axis to reverse 5-FU resistance. The RRM1-USP19-NEDD4 axis represents a novel therapeutic target for overcoming chemoresistance in CRC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343933","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":"ITGB5 promotes immune escape in hepatocellular carcinoma by regulating PD-L1 through SETDB1/Hippo signaling pathway.","authors":"Mengmeng Wang, Li Gu, Ruijiang Zeng, Chen Zhang, Jing Zhang, Pian Liu","doi":"10.1007/s13402-026-01240-3","DOIUrl":"10.1007/s13402-026-01240-3","url":null,"abstract":"<p><strong>Background: </strong>The overall response rate to immune checkpoint inhibitors (ICIs) in HCC patients remains low. It has been reported that ITGB5 correlate with the immune infiltration of tumors. Our previous study showed that ITGB5 reduces HCC cell sensitivity to TKIs. However, the role of ITGB5 in HCC immunity remains unclear.</p><p><strong>Methods: </strong>The mRNA and protein expression of ITGB5, SETDB1, LATS2 and PD-L1 in hepatocellular carcinoma cells and tissues were determined by RT-qPCR, Western Blot and Immunofluorescence. PD-L1 positive cells were analyzed by flow cytometry. The relationship between ITGB5 expression and immune cell infiltration was investigated by applying TIMER database. The effects of ITGB5 on the immune response and immunotherapy of hepatocellular carcinoma were determined by constructing a spontaneous tumor model of hepatocellular carcinoma and a subcutaneous tumor model in mice.</p><p><strong>Results: </strong>ITGB5 promotes immune escape in HCC by activating PD-L1 expression, a target gene of the Hippo signaling pathway, through the SETDB1-LATS2 axis. ITGB5 reduces the susceptibility of HCC to immunotherapy. Importantly, ITGB5 knockdown enhanced the efficacy of PD-1 therapy in mice harboring HCC.</p><p><strong>Conclusions: </strong>ITGB5 plays an important role in the immune response of hepatocellular carcinoma. ITGB5 may serve as a biomarker for evaluating immunotherapy efficacy and represent a promising therapeutic target for HCC treatment, either alone or in combination with anti-PD-1 antibodies.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343593","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":"Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.","authors":"Xiangyu Zhang, Yutong Zhao, Cheng Qin, Zeru Li, Yiping Xie, Yutong Yan, Tianyu Li, Lirui Huang, Haoyu Shi, Weibin Wang","doi":"10.1007/s13402-026-01251-0","DOIUrl":"10.1007/s13402-026-01251-0","url":null,"abstract":"<p><p>Acinar-ductal metaplasia (ADM) represents a dynamic and reversible cellular adaptation in the pancreas, whereby acinar cells dedifferentiate and transdifferentiate into duct-like cells in response to inflammatory, metabolic, and environmental stressors. While transient ADM facilitates tissue repair after acute injury, persistent stimuli-including chronic pancreatitis, metabolic dysregulation, obesity, diabetes, smoking, and oncogenic KRAS mutations-stabilize ADM and promote progression to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC). ADM is orchestrated by integrated signaling networks involving TGF-β/SMAD, EGFR-KRAS-MAPK, PI3K-AKT-mTOR, Notch, Wnt/β-catenin, and JAK/STAT3, which regulate dedifferentiation, proliferation, survival, and fibrosis. Inflammatory cells, particularly macrophages and eosinophils, and pro-inflammatory cytokines such as IL‑6, IL‑18, and TNF‑α further amplify ADM and create a tumor-promoting microenvironment. Single-cell analyses reveal that ADM encompasses heterogeneous cell states with distinct lineage trajectories, determining reversibility or pre-neoplastic transformation. Pharmacological interventions, including HDAC inhibitors, JAK/STAT3 inhibitors, metformin, and anti-inflammatory agents, show potential in preventing or reversing ADM. Understanding the complex molecular, cellular, and environmental regulation of ADM provides critical insights into pancreatic regeneration and early tumorigenesis and offers a framework for developing targeted strategies for the prevention and treatment of pancreatitis and PDAC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350682","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":"Reverse cardio-oncology: neuroendocrine axis activation and cardiovascular-disease-derived factors synergistically remodel the tumor microenvironment.","authors":"Siyu Ji, Nan Zhang, Xin Hu","doi":"10.1007/s13402-026-01243-0","DOIUrl":"10.1007/s13402-026-01243-0","url":null,"abstract":"<p><p>Cardiovascular disease and cancer are increasingly recognized as biologically interconnected conditions with a bidirectional relationship. In addition to the well-established cardiotoxic effects of cancer therapies, accumulating epidemiological and experimental evidence suggests that cardiovascular disease may influence cancer initiation, progression, and metastasis, a concept referred to as reverse cardio-oncology. However, the mechanisms linking cardiovascular pathology to tumor microenvironment remodeling remain incompletely defined and are likely to involve multiple interacting systemic and local pathways. In this review, we summarize current evidence regarding the potential contribution of cardiovascular stress, neuroendocrine activation, metabolic dysregulation, impaired oxygen delivery, physical inactivity, and cardiovascular disease-derived secretory factors to tumor microenvironment remodeling. Particular attention is given to vascular endothelial growth factor, extracellular vesicles, reactive oxygen species, and inflammatory cytokines, which may act as interconnected mediators of angiogenesis, immune suppression, oxidative stress, and metastatic progression. We further discuss how these pathways may converge within a broader hierarchical and network-based framework, while emphasizing that much of the current mechanistic evidence remains derived from observational studies, animal models, and in vitro systems. Finally, we highlight therapeutic implications, including modulation of neuroendocrine and inflammatory signaling, and propose future directions involving human tissues, clinical samples, and heart-cancer-on-a-chip platforms. Overall, this review aims to provide a balanced synthesis of current knowledge and unresolved questions in reverse cardio-oncology, with the goal of supporting more integrated investigation of cardiovascular disease-cancer interactions.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343919","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":"Tumor lymph node metastasis chip reveals that the NECTIN3-TIGIT axis promotes melanoma metastasis by enhancing treg cell function and inducing CD8⁺ T cell exhaustion.","authors":"Cuihao Song, Wenwei Zhu, Yaolin Li, Yuhan Ji, Xiaoling Liu, Yingjie Zhang, Xiaoning Zhang, Fangfang Wei, Hexi Yang, Likeng Liang, Shuyan Huang, Chengxin Li, Yong Zhou","doi":"10.1007/s13402-026-01246-x","DOIUrl":"10.1007/s13402-026-01246-x","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the role and molecular mechanism of the NECTIN3-TIGIT axis in melanoma lymph node metastasis.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed on human primary melanoma and lymph node metastatic tissues. A tumor lymph node metastasis-on-a-chip model incorporating vascular, lymphatic, and dual-tumor modules was constructed, along with in vitro coculture systems using CD8⁺ T cells and regulatory T cells. Functional blockade was achieved via NECTIN3 knockdown, TIGIT inhibitor (Tiragolumab), and combined antiPD1 therapy.</p><p><strong>Results: </strong>The NECTIN3-TIGIT axis was identified as a core immune ligand-receptor pair in the highmetastasis subgroup, associated with increased regulatory T cell infiltration and CD8⁺ T cell exhaustion. Both NECTIN3 and TIGIT expression were significantly elevated in metastatic lesions and correlated with reduced overall survival. The chip model recapitulated melanoma lymphatic migration and confirmed the immunosuppressive microenvironment. Mechanistically, the NECTIN3-TIGIT axis induced CD8⁺ T cell exhaustion via the SHIP-1/TRAF6 pathway and promoted regulatory T cell activation by inhibiting AKT/mTORC1 signaling. NECTIN3 knockdown or Tiragolumab treatment suppressed tumor lymphatic migration, while combined antiPD1 and Tiragolumab most effectively reversed T cell exhaustion, impaired regulatory T cell function, and reduced metastasis.</p><p><strong>Conclusion: </strong>The NECTIN3-TIGIT axis promotes melanoma lymph node metastasis by remodeling the immunosuppressive microenvironment. Combined blockade of NECTIN3-TIGIT and PD1 pathways represents a promising therapeutic strategy.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315956","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":"Tasimelteon inhibits glioma proliferation by inducing ferroptosis via the SP1/ACSL4 pathway.","authors":"Yi Chen, Jicheng Li, Huilan Yang, Haiyang Liang, Ji Shi, Quan Li, Qiang Liu, Jia Liu, Xuanming Zhang, Huizhe Xu, Haozhe Piao","doi":"10.1007/s13402-026-01244-z","DOIUrl":"10.1007/s13402-026-01244-z","url":null,"abstract":"<p><strong>Purpose: </strong>Gliomas are aggressive tumors with poor treatment outcomes. Tasimelteon, an FDA-approved melatonin receptor agonist with favorable blood-brain barrier penetration, has unexplored anti-tumor potential. This study investigated whether Tasimelteon inhibits glioma proliferation through ferroptosis induction.</p><p><strong>Methods: </strong>Cell viability, colony formation, and immunofluorescence were employed to assess the effects of Tasimelteon on glioma cells. Ferroptosis was assessed by measuring lipid peroxidation markers (MDA, 4-HNE, BODIPY 581/591 C11) and ROS levels, and mitochondrial damage was detected by TEM. Mechanisms were examined through Western blotting, qPCR, dual-luciferase reporter assays, site-directed mutagenesis and molecular docking. In vivo, LN229-Luc glioma cells were orthotopically injected into mouse brains, followed by Tasimelteon treatment. Tumor growth was monitored by bioluminescence imaging, and body weight and survival were recorded. Systemic toxicity was evaluated through H&E staining of major organs.</p><p><strong>Results: </strong>Tasimelteon decreased glioma cell viability and colony formation in dose- and time-dependent manners. Mechanistically, Tasimelteon induced ferroptosis, characterized by elevated lipid peroxidation markers (MDA, 4-HNE) and ROS levels, along with mitochondrial damage observed by TEM. This process was accompanied by ACSL4 upregulation. Further investigation revealed that Tasimelteon bound to SP1 at Gln465 and Leu467 residues, stabilizing the protein and enhancing ACSL4 transcription, independent of MT1/MT2 receptor activation. In orthotopic glioma models, Tasimelteon suppressed tumor growth by inducing ferroptosis and prolonged survival without systemic toxicity.</p><p><strong>Conclusion: </strong>Tasimelteon inhibits glioma growth by inducing ferroptosis via the SP1/ACSL4 pathway, offering a novel therapeutic approach.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301125","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":"The O-GlcNAc modification of PRRC2C at S2238 promotes SG formation and nasopharyngeal carcinoma metastasis.","authors":"Haimeng Yin, Shumei Ding, Han Deng, Ying Shan, Yumo Han, Yuntong Liu, Juping Sheng, Bo You","doi":"10.1007/s13402-026-01242-1","DOIUrl":"10.1007/s13402-026-01242-1","url":null,"abstract":"<p><strong>Purpose: </strong>Metastasis remains the leading cause of mortality in patients with nasopharyngeal carcinoma (NPC), yet its precise mechanism has not been fully elucidated.</p><p><strong>Methods: </strong>In this study, we established high metastatic (HM) and low metastatic (LM) sublines of NPC cells using the Transwell system, aiming to systematically investigate the metabolic reprogramming events that occur during NPC metastasis.</p><p><strong>Results: </strong>Metabolomics sequencing results revealed that HM NPC cells have undergone metabolic profile remodeling, leading to increased levels of O-linked N-acetylglucosamine (O-GlcNAc) modification substrates UDP-GlcNAc and UDP-GalNAc, consequently, HM cells exhibited a significantly higher global O-GlcNAc modification level than LM cells. Through the construction of OGT-overexpressing cells and O-GlcNAc modification sequencing, we identified a significant elevation in the O-GlcNAcylation level of Proline-Rich Coiled-Coil 2 C (PRRC2C), a protein associated with stress granule (SG) formation. By transfecting PRRC2C WT and PRRC2C S2238A (serine 2238-to-alanine substitution) plasmids, we mimicked the characteristics of HM and LM cells and found that the O-GlcNAc modification of PRRC2C at S2238 site could promote the formation of SG at mitochondrial platform. Mechanistically, NPC cells transfected with the PRRC2C S2238A plasmids maintained mitochondrial functional homeostasis, evidenced by intact mitochondrial membrane potential and balanced mitochondrial dynamics compared to PRRC2C WT cells. In the nude mice orthotopic transplantation model, the use of epigallocatechin gallate (EGCG) could modulate the metastatic potential of HM cells via the inhibition of SGs.</p><p><strong>Conclusion: </strong>Collectively, this study identifies targeting O-GlcNAcylation of PRRC2C at S2238 and SG formation as a promising therapeutic strategy for patients with metastatic NPC. REGISTRY AND THE REGISTRATION NO.</p><p><strong>Of the study/trial: </strong>N/A.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249562","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}