Cell Death & Disease最新文献

{"title":"SUMOylation of the lysine-less tumor suppressor p14ARF counters ubiquitylation-dependent degradation.","authors":"Ahmed El Motiam, Yanis H Bouzaher, Haifen Chen, Rocío Seoane, Santiago Vidal, María Blanquer, Rocío M Tolosa, Beatriz Rodríguez-Lemus, José A Herrera-Gavilán, Anxo Vidal, Ignacio Palmero, Manuel S Rodríguez, James D Sutherland, Rosa Barrio, Dimitris Xirodimas, Manuel Collado, Rod Bremner, Carmen Rivas","doi":"10.1038/s41419-025-07854-z","DOIUrl":"https://doi.org/10.1038/s41419-025-07854-z","url":null,"abstract":"<p><p>p14ARF is a lysine-less tumor suppressor that enhances SUMOylation of its interactors. Although p14ARF is known to interact with the E2 SUMO conjugating enzyme UBC9, the link between ARF and SUMOylation is poorly understood and the potential impact of SUMOylation on p14ARF is unknown. Here we show that SUMO2 conjugates to the N-terminus of p14ARF and stabilizes it. Either depleting UBC9 or pharmacologically inhibiting SUMOylation, induces p14ARF degradation. In contrast, blocking ubiquitination or NEDDylation, with TAK-243 or MLN4924/Pevonedistat respectively, increases p14ARF SUMOylation and restores p14ARF levels when SUMOylation is blocked. Treatment with MLN4924 also causes p14ARF-dependent mRNA upregulation of the SUMOylation components SUMO1, SUMO2, and UBC9, globally augmenting SUMOylation. Finally, p14ARF contributes to MLN4924-driven cytotoxicity of prostate cancer cells. Our results provide evidence that, despite lacking lysine, p14ARF is SUMOylated and this modification is critical to counter ubiquitin driven degradation and establishes a new link between inhibition of NEDDylation and SUMOylation.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"519"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation of METTL3 drives hepatocellular carcinoma progression by upregulating MCM10 expression in an m6A-IGF2BP3-dependent manner.","authors":"Zhen Chen, Jiaxin Yin, Zhongqi Feng, Yanlai Zhang, Li Liang, Xiaojun Wang, Kai Wang, Ni Tang","doi":"10.1038/s41419-025-07844-1","DOIUrl":"https://doi.org/10.1038/s41419-025-07844-1","url":null,"abstract":"<p><p>The m6A methyltransferase METTL3 is a key regulator of RNA m6A modification, which plays a critical role in cancer development. Despite the significance of METTL3 in hepatocellular carcinoma (HCC), its post-translational modifications and their functional implications in HCC remain poorly understood. The present study reveals that METTL3 undergoes O-GlcNAcylation, which enhances its stability and promotes HCC progression. Specific O-GlcNAcylation sites (T186/S192/S193) in METTL3 are identified. O-GlcNAc modification reduces METTL3 ubiquitination, thereby increasing protein stability, and enhances its interaction with WTAP, thereby sustaining m6A levels in hepatoma cells. Notably, METTL3 O-GlcNAcylation upregulates the expression of minichromosome maintenance protein 10 (MCM10) by stabilizing its mRNA via an m6A-IGF2BP3-dependent manner. Targeting METTL3 O-GlcNAcylation with designed peptides effectively inhibits HCC growth both in vitro and in vivo. Collectively, our findings provide insights into the regulatory role of O-GlcNAcylation in modulating the m6A epitranscriptome and suggest the potential therapeutic relevance of targeting METTL3 O-GlcNAcylation in HCC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"518"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CENPT prevents renal cell carcinoma against ferroptosis by enhancing the synthesis of glutathione.","authors":"Han Yang, Zongliang Zhang, Ninghan Feng, Kai Zhao, Yulian Zhang, Xinbao Yin, Guanqun Zhu, Zhenlin Wang, Xuechuan Yan, Xueyu Li, Zhaofeng Li, Qinglei Wang, Yixin Qi, Peng Zhao, Tianzhen He, Ke Wang","doi":"10.1038/s41419-025-07848-x","DOIUrl":"https://doi.org/10.1038/s41419-025-07848-x","url":null,"abstract":"<p><p>Cancer is characterized by chromosomal instability (CIN), which leads to tumor heterogeneity and other malignant features. CIN is caused by abnormal centromere and kinetochore function, which results in aneuploidy, rearrangements, and micronucleus production. Centromere and kinetochore gene misexpression plays a vital role in tumor progression. Here we show that Centromere Protein T (CENPT) is highly expressed in renal carcinoma (RCC) and promotes the tumor proliferation and metastasis of RCC. CENPT is found to be critical for regulating the glutathione (GSH) metabolism pathway because it interacts with γ-glutamyl-cysteine ligase catalytic subunit (GCLC), consequently reducing reactive oxygen species levels and inhibiting ferroptosis. Mechanistically, CENPT increases the catalytic activity of GCLC by directly binding to GCLC ∆213-424aa competitively with glutamate-cysteine ligase modifier subunit (GCLM), consequently induces the GSH synthesis. In turn, GSH increases CENPT expression via transcriptional regulation mediated by the transcription factor ATF2, forming a CENPT-GCLC-GSH feedback loop that enhances the pro-carcinogenic effect of this axis in RCC. Our study identifies CENPT a potential target for RCC via forming a CENPT-GCLC-GSH feedback loop to inhibit ferroptosis. This may support a promising treatment strategy for RCC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"517"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-induced STUB1-GOT2 axis promotes aspartate synthesis and mitochondrial dysfunction in bladder cancer.","authors":"Yunqiang Xiong, Qianxi Dong, Hongji Hu, Zhongqi Li, Xiangpeng Zhan, Fuchun Zheng, Hao Wan, Jiahao Liu, Shuyu Wu, Wang Pan, Ruize Yuan, Jing Xiong, Ju Guo, Songhui Xu, Bin Fu","doi":"10.1038/s41419-025-07840-5","DOIUrl":"https://doi.org/10.1038/s41419-025-07840-5","url":null,"abstract":"<p><p>Aberrant glucose metabolism, a characteristic of malignant tumors, contributes to the development and progression of bladder cancer (BCa). However, the underlying mechanism by which aberrant glucose metabolism promotes BCa progression is still incompletely understood. Here, we demonstrate that low levels of STUB1 are associated with worse progression and poor prognosis of BCa patients. STUB1 overexpression attenuates BCa cell proliferation, migration and amino acid metabolism, especial aspartate metabolism. Mechanistically, we identify that STUB1 induces K6- and K48-linked polyubiquitination of GOT2 at K73 lysine residue to decrease its stability, which attenuates mitochondrial aspartate (Asp) synthesis and regulates mitochondrial dysfunction. GOT2 was significantly up-regulated in BCa tissues and negatively associated with STUB1 expression. Furthermore, we reveal that high glucose stress promotes Asp synthesis and tumor growth through STUB1-GOT2 axis. Collectively, our findings identify that STUB1-GOT2 axis is an important regulator for maintaining Asp synthesis and mitochondrial function in BCa cell growth, which highlights that targeting STUB1-GOT2 axis could be a valuable strategy to ameliorate BCa progression by inhibiting amino acid metabolic function.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"516"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00622 transcriptionally promotes RRAGD to repress mTORC1-modulated autophagic cell death by associating with BTF3 in cutaneous melanoma.","authors":"Can Li, Ke Wang, Lei Zhao, Jieyu Liu, Yi Jin, Chunting Zhang, Minna Xu, Min Wang, Yanjie Kuang, Jun Liu, Liang Zhou, Qian Wen","doi":"10.1038/s41419-025-07828-1","DOIUrl":"https://doi.org/10.1038/s41419-025-07828-1","url":null,"abstract":"<p><p>Autophagy plays critical and complicated roles in tumors. As the central hub of nutrient signaling and cell growth, mTOR constitutes mTORC1 to be the main gateway for modulating autophagy. Yet, the regulatory mechanisms of mTORC1-regulated autophagy in tumors are not fully deciphered. Here, we report a novel long noncoding RNA, LINC00622, which modulates mTORC1-regulated autophagy in cutaneous melanoma. Functionally, LINC00622 acts as a pro-oncogenic factor to promote proliferation, colony formation, migration and invasion in melanoma while suppressing cell death. Mechanistically, LINC00622 associates with and recruits BTF3 to transcriptionally enhance RRAGD expression for activating mTORC1 and thus inhibiting autophagic cell death, which contributes to the development of cutaneous melanoma. Our findings not only demonstrated the oncogenic role of LINC00622 via RRAGD/mTORC1 axis to repress autophagic cell death in cutaneous melanoma, but also offer novel treatment targets for melanoma therapy.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"515"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-translational modification of transcription factors: perspectives in vascular medicine.","authors":"Elena Astanina, Elisa Setten, Francesco Boccalatte, Federico Bussolino, Valentina Comunanza","doi":"10.1038/s41419-025-07832-5","DOIUrl":"https://doi.org/10.1038/s41419-025-07832-5","url":null,"abstract":"<p><p>In vascular diseases, the perturbation of key metabolic pathways is extensively studied and recognized as both a causal factor and a consequence in disease onset and progression. Similarly, the dysregulation of the transcriptional landscape within vascular unit components (endothelial and vascular smooth muscle cells) is a pivotal aspect of disease pathogenesis. Metabolite-induced post-translational modifications of transcription factors significantly modulate their functionality, leading to drastic changes in transcriptional outcomes. This review offers a new perspective by elucidating the link between metabolic alterations and metabolite-induced post-translational modifications of transcription factors integral to the pathogenesis of four paradigmatic vascular pathologies: atherosclerosis, diabetes, pulmonary hypertension and tumor angiogenesis.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"520"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATRA upregulates OTUD6B to recruit CD8⁺ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis.","authors":"Jinglei Li, Kunpeng Huang, Bing Yang, Xia Hu, Bosheng Mei, Xiang Cheng, Xin Zhong, Chuyi Cao, Zihan Chen, Hui Wang, Jinxiang Zhang","doi":"10.1038/s41419-025-07837-0","DOIUrl":"https://doi.org/10.1038/s41419-025-07837-0","url":null,"abstract":"<p><p>OTU deubiquitinase 6B (OTUD6B) study in tumors is gradually increasing; however, studies on the role of OTUD6B in colorectal cancer (CRC) are rare. OTUD6B was overexpressed in some human CRC and liver metastasis samples. Although OTUD6B facilitated migration and invasion in CRC cells, it exhibited opposite effects on liver metastasis in immunodeficient and immunocompetent mice. We demonstrated that Otud6b enhanced metastasis in nude mice, but it recruited more CD8⁺ T cell infiltration in colorectal liver metastasis (CRLM) mouse model of C57BL/6J to inhibit CRLM through upregulating Cxcl11. Furthermore, we demonstrated that OTUD6B deubiquitinated and stabilized DDX5. Ectopically expressed DDX5 facilitated transcription factor STAT3 activation by resolving the RNA G-quadruplex structure of STAT3, resulting in a higher level of CXCL11 transcription and an increase in tumor-infiltrating CD8⁺ T cells. All-trans retinoic acid inhibited CRLM by upregulating OTUD6B.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"521"},"PeriodicalIF":8.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma.","authors":"Xiaoxiao Li, Fujia Lu, Jie Zhou, Xiong Li, Yan Li, Weijie Ye, Jing Li, Liguo Yang, Shi Tang, Yuhan Zhou, Songlin Yin, Yuan Gao, Haotian Shang, Tengfei Chao, Xiang Cheng, Qian Chu, Weimin Wang","doi":"10.1038/s41419-025-07839-y","DOIUrl":"10.1038/s41419-025-07839-y","url":null,"abstract":"<p><p>Tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced hepatocellular carcinoma (HCC). However, their therapeutic efficacy is often limited by drug resistance, primarily driven by tumoral intrinsic mechanisms. In this study, we demonstrate that IFNγ in the tumor microenvironment can potentiate TKI response, and that ablation of IFNγ receptor on HCC cells leads to TKI resistance in vivo. Mechanistically, IFNγ synergizes with TKI to induce GSDME-mediated pyroptosis of HCC cells. The PERK-mediated unfolded protein response (UPR) protects HCC cells from TKI-induced pyroptosis. IFNγ attenuates PERK activation by inducing the expression of PDIA1, which alleviates the stress of protein unfolding. In vivo, PERK inhibition augments TKI therapy, and elevated PERK expression correlates with poor overall survival of patients with HCC. Moreover, IFNγ-producing CD8⁺ T cells can potentiate TKI efficacy. Combining PD-1 blockade to activate T-cell response with TKI therapy synergistically suppresses the growth of GSDME-expressing HCC tumors, which is further enhanced by the PERK inhibitor. Our findings reveal how IFNγ signaling modulates TKI response and demonstrate the potential of a sequential combination of ICB-mediated immunotherapy and TKI therapy for patients with GSDME⁺ HCC. T cell-derived IFNγ enhances TKI-induced pyroptosis in HCC. Mechanistic illustration of IFNγ secreted from CD8⁺ T cells enhancing TKI-induced GSDME-mediated pyroptosis in hepatocellular carcinoma via suppression of the PERK pathway. Created with BioRender.com.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"512"},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invasive lobular carcinoma: integrated multi-omics analysis reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance.","authors":"Annapurna Gupta, Fouad Choueiry, Jesse Reardon, Nikhil Pramod, Anagh Kulkarni, Eswar Shankar, Steven T Sizemore, Daniel G Stover, Jiangjiang Zhu, Bhuvaneswari Ramaswamy, Sarmila Majumder","doi":"10.1038/s41419-025-07788-6","DOIUrl":"10.1038/s41419-025-07788-6","url":null,"abstract":"<p><p>Invasive Lobular Carcinoma (ILC), a distinct subtype of breast cancer, is hallmarked by E-Cadherin loss, slow proliferation, and strong hormone receptor positivity. ILC faces significant challenges in clinical management due to advanced stage at diagnosis, late recurrence, and development of resistance to endocrine therapy - a cornerstone of ILC treatment. To elucidate the mechanisms underlying endocrine resistance in ILC, ILC cell lines (MDA-MB-134-VI, SUM44PE) were generated to be resistant to tamoxifen, a selective estrogen receptor modulator. The tamoxifen-resistant (TAMR) cells exhibit a 2-fold increase in tamoxifen IC₅₀ relative to parental cells. Metabolomics and RNA-sequencing revealed deregulation of alanine, aspartate, and glutamate metabolism, purine metabolism, and arginine and proline metabolism in TAMR cells. Among the fifteen commonly dysregulated genes in these pathways, low argininosuccinate synthase (ASS1) expression was identified in the TAMR cells and was significantly correlated with poor outcome in ILC patients, specifically in the context of endocrine therapy. Our study reveals methylation-mediated silencing of ASS1 in TAMR cells as a likely mechanism of downregulation. Demethylation restored ASS1 expression and correspondingly reduced tamoxifen IC₅₀ toward parental levels. Nucleic acid biosynthesis is augmented in TAMR cells, evidenced by an increase in nucleotide intermediates. Both TAMR cell lines demonstrated increased expression of several nucleic acid biosynthesis enzymes, including PAICS, PRPS1, ADSS2, CAD, and DHODH. Furthermore, CAD, the key multifunctional protein of the de novo pyrimidine biosynthesis pathway, is differentially activated in TAMR cells. Treating TAMR cells with Decitabine, a demethylating agent, or Farudodstat, a pyrimidine biosynthesis inhibitor, markedly augmented the efficacy of tamoxifen. Collectively, our study unveils ASS1 downregulation as a novel mechanism underlying acquired tamoxifen resistance in ILC and establishes a metabolic link between ASS1 and nucleic acid biosynthesis. Restoring ASS1 expression or inhibiting pyrimidine biosynthesis reinstated tamoxifen sensitivity. ASS1 could be a potential biomarker and therapeutic target in tamoxifen-resistant ILC patients, warranting further investigation.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"514"},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate induces ferroptosis in diffuse large B-cell lymphoma cells by targeting PRDX1 and PRDX2.","authors":"Xiaohui Liu, Liyi Zeng, Jing Liu, Yulun Huang, Hua Yao, Jinman Zhong, Jiewen Tan, Xuenjuan Gao, Dan Xiong, Langxia Liu","doi":"10.1038/s41419-025-07822-7","DOIUrl":"10.1038/s41419-025-07822-7","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL), the most prevalent non-Hodgkin lymphoma (NHL), is characterized by rapid growth and an unfavorable prognosis. Artesunate (ART), a derivative of Artemisinin, is a widely recognized antimalarial drug that displays notable antitumor properties across diverse cancers. Our previous studies have demonstrated ART's capacity to inhibit DLBCL progression via the induction of ferroptosis. However, its direct target molecules mediating this effect remained elusive. In this study, using small molecule (SM) pull-down combined with mass spectrometry analysis (LC-MS/MS), we have identified two peroxidases, PRDX1 and PRDX2, which play key roles in cellular antioxidant processes, as potential target proteins for ART in the treatment of DLBCL cells. Subsequently, we utilized cellular thermal shift assay (CETSA), fluorescence titration, circular dichroism (CD) spectroscopy, molecular docking, and pull-down assays to confirm that ART directly binds to PRDX1 and PRDX2. The Gly4 residue on PRDX1 and the Arg7 and Thr120 residues on PRDX2 are respectively responsible for ART binding. Knockdown of either PRDX1 or PRDX2 not only reproduced the ferroptosis-inducing effect of ART but also significantly attenuated the sensitivity of cells to ART. Furthermore, PRDX2 overexpression attenuated the reactive oxygen species (ROS) production and cytotoxicity in cells treated with ART. Consistently, ART selectively killed DLBCL cells, sparing normal cells thanks to their lower PRDX1 expression. In nude mice bearing U2932 xenografts, ART treatment inhibited significantly tumor growth and improved liver function without causing cardiac or hepatic toxicity, which was associated with an elevated level of ferroptosis and a significantly decreased peroxidase activity. Collectively, our findings elucidate the molecular mechanism by which ART induces ferroptosis through direct interaction with PRDX1 or PRDX2 and highlight these PRDXs as potential therapeutic targets for DLBCL.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"513"},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}