Cell Death & Disease最新文献_第8页

Editorial Expression of Concern to: TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133⁺ A549 cell fraction. 编辑关注的表达：TGF-β1暴露诱导A549细胞系的CSCs和非CSCs的上皮向间质转化，导致CD133+ A549细胞部分的迁移能力增加。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-02 DOI: 10.1038/s41419-025-07780-0

V Tirino, R Camerlingo, K Bifulco, E Irollo, R Montella, F Paino, G Sessa, M V Carriero, N Normanno, G Rocco, G Pirozzi

引用次数: 0

AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5. AKR1C3通过抑制trim21介导的HSPA5泛素化来抑制铁下垂，从而增强食管腺癌的放射耐药。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-02 DOI: 10.1038/s41419-025-07773-z

Feng Ju, Jialei Weng, Ningbo Fan, Zhefang Wang, Chenghui Zhou, Xinlei Zhao, Nellie Horstmann, Xiaolin Wu, Sascha Hoppe, Bo You, Keying Li, Jianxin Duan, Margarete Odenthal, Axel M Hillmer, Alexander Quaas, Christiane J Bruns, Yue Zhao

{"title":"AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5.","authors":"Feng Ju, Jialei Weng, Ningbo Fan, Zhefang Wang, Chenghui Zhou, Xinlei Zhao, Nellie Horstmann, Xiaolin Wu, Sascha Hoppe, Bo You, Keying Li, Jianxin Duan, Margarete Odenthal, Axel M Hillmer, Alexander Quaas, Christiane J Bruns, Yue Zhao","doi":"10.1038/s41419-025-07773-z","DOIUrl":"10.1038/s41419-025-07773-z","url":null,"abstract":"Esophageal adenocarcinoma (EAC) is the predominant subtype of esophageal cancer (EC) in high-income countries, and radioresistance is one of the key factors for the poor prognosis. In this study, we successfully established a radioresistant EAC in vitro model. Aldo-keto reductase 1C3 (AKR1C3) was identified as a promising regulator of radioresistance by RNA-seq analysis and subsequent functional studies. Through integrated analyses of scRNA-seq and TCGA datasets, we found that AKR1C3 was likely to enhance radioresistance by inhibition of ferroptosis. Indeed, analysis of the lipid ROS level by C11-Bodipy staining and the result of transmission electron microscopy revealed that AKR1C3 could prevent EAC cells from ferroptosis. Mechanistically, AKR1C3 binds to the nucleotide-binding domain of HSPA5, thereby inhibiting the E3 ligase TRIM21-induced ubiquitin-dependent proteasomal degradation of HSPA5, which further stabilizes GPX4, thus inhibiting ferroptosis. Importantly, AKR1C3 inhibitor resensitized the EAC patient-derived organoids to radiotherapy. In conclusion, this study highlights AKR1C3 as a regulator of radioresistance and a potential therapeutic target in EAC.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"483"},"PeriodicalIF":8.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552445","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}

引用次数: 0

FGFR inhibitors promote the autophagic degradation of IFN-γ-induced PD-L1 and alleviate the PD-L1-mediated transcriptional suppression of FGFR3-TACC3 in non-muscle-invasive bladder cancer. FGFR抑制剂促进IFN-γ诱导的PD-L1的自噬降解，减轻PD-L1介导的FGFR3-TACC3在非肌肉侵袭性膀胱癌中的转录抑制。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-02 DOI: 10.1038/s41419-025-07821-8

Yu-Chen Lin, Cheng-Ying Chu, Tsung-Han Hsieh, Bo-Jyun Lin, Jing-Ping Liou, Yun Yen, Chun-Han Chen

{"title":"FGFR inhibitors promote the autophagic degradation of IFN-γ-induced PD-L1 and alleviate the PD-L1-mediated transcriptional suppression of FGFR3-TACC3 in non-muscle-invasive bladder cancer.","authors":"Yu-Chen Lin, Cheng-Ying Chu, Tsung-Han Hsieh, Bo-Jyun Lin, Jing-Ping Liou, Yun Yen, Chun-Han Chen","doi":"10.1038/s41419-025-07821-8","DOIUrl":"10.1038/s41419-025-07821-8","url":null,"abstract":"Bladder cancer (BC) is the second most prevalent genitourinary malignancy worldwide. Treatment options remain limited for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). Up to 70% of NMIBC cases harbor fibroblast growth factor receptor 3 (FGFR3) alterations, and FGFR inhibition has shown potential to enhance the efficacy of immune checkpoint inhibitor (ICI). Interferon (IFN)-γ, a cytokine produced by activated T cells and associated with better response to immunotherapy in BC, is a key inducer of PD-L1 expression in the tumor microenvironment. However, the interaction between FGFR inhibitors and IFN-γ-induced PD-L1 expression in FGFR3-activated NMIBC cells remains unclear. Here, we show that FGFR inhibitors significantly reduced IFN-γ-induced PD-L1 expression in NMIBC cells harboring FGFR3-TACC3 fusions. Mechanistically, FGFR inhibitors restored IFN-γ-suppressed SIRT1 expression, promoted LC3B deacetylation and nuclear export, and enhanced autophagy-lysosomal degradation of PD-L1. Blocking autophagy, overexpression SIGMAR1, or inhibiting lysosomal activity significantly reversed PD-L1 degradation. Notably, we demonstrate for the first time that IFN-γ-induced PD-L1 directly binds to the FGFR3 promoter and represses FGFR3-TACC3 transcription-an effect that can be rescued by FGFR inhibitors or PD-L1 knockdown. Functionally, FGFR inhibitors ameliorated PD1/PD-L1-mediated T cell suppression in co-culture assays. Together, these findings highlight a novel mechanism by which FGFR inhibitors suppress IFN-γ-induced PD-L1 via autophagy and suggest a potential strategy to improve ICI therapy in FGFR3-altered NMIBC.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"485"},"PeriodicalIF":8.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552447","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}

引用次数: 0

SLC44A2 negatively regulates mitochondrial fatty acid oxidation to suppress colorectal progression by blocking the MUL1-CPT2 interaction. SLC44A2负调控线粒体脂肪酸氧化，通过阻断MUL1-CPT2相互作用抑制结直肠进展。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07781-z

Ying Yang, Longlong Zheng, Jiaxing He, Tao Wu, Haicheng Yang, Bo Zhang, Shuai Zhou, Yueyue Lu, Xianli He, Jibin Li, Nan Wang

{"title":"SLC44A2 negatively regulates mitochondrial fatty acid oxidation to suppress colorectal progression by blocking the MUL1-CPT2 interaction.","authors":"Ying Yang, Longlong Zheng, Jiaxing He, Tao Wu, Haicheng Yang, Bo Zhang, Shuai Zhou, Yueyue Lu, Xianli He, Jibin Li, Nan Wang","doi":"10.1038/s41419-025-07781-z","DOIUrl":"10.1038/s41419-025-07781-z","url":null,"abstract":"The dependence of cancer cells on mitochondrial metabolism has been revealed in various cancer types. However, the mechanisms underlying this metabolic remodeling remain largely unclear. Solute carrier family 44 member 4 (SLC44A2) is a mitochondrial membrane-localized transmembrane protein belonging to the choline transporter-like protein family. Recently, it was reported that deletion of SLC44A2 impairs adhesion and increases proliferation in cultured lung mesenchymal cells. This finding implies that SLC44A2 may play a role in the malignant phenotypes of human cancers. However, the effects of SLC44A2 on malignant phenotypes and mitochondrial metabolism in human cancers remain unexplored. In the present investigation, we observed a significant reduction in SLC44A2 expression in colorectal cancer (CRC), and low SLC44A2 expression was closely associated with poorer survival of CRC patients. Functional assays demonstrated that SLC44A2 suppressed CRC growth and metastasis both in vitro and in vivo. Mechanistically, SLC44A2 inhibits mitochondrial fatty acid oxidation, thereby reducing energy supply and increase ROS stress. This effect is achieved by promoting mitochondrial E3 ubiquitin ligase 1 (MUL1)-regulated degradation of carnitine palmitoyltransferase 2 (CPT2) via enhancing the interaction between MUL1 and CPT2, without increasing MUL1 expression, which ultimately contributes to the proliferation and metastasis of CRC. Together, SLC44A2 functions as a critical tumor suppressor in CRC and potential therapeutic target in the treatment of this malignancy.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"468"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539121","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}

引用次数: 0

p66Shc deletion confers apoptotic resistance to loss of EGFR-ERK signalling in neural stem cells. p66Shc缺失赋予神经干细胞对EGFR-ERK信号丢失的凋亡抗性。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07778-8

Andrew M Powell, Robert C Cumming, Dean H Betts

{"title":"p66Shc deletion confers apoptotic resistance to loss of EGFR-ERK signalling in neural stem cells.","authors":"Andrew M Powell, Robert C Cumming, Dean H Betts","doi":"10.1038/s41419-025-07778-8","DOIUrl":"10.1038/s41419-025-07778-8","url":null,"abstract":"Growth factor signalling, through epidermal growth factor (EGF) and its receptor (EGFR), governs neural stem cell (NSC) proliferation, differentiation, and survival. The Src Homology and Collagen (SHC1) adaptor protein mediates EGFR survival-signalling in NSCs via its two shorter isoforms. However, the role of its longest isoform, p66Shc, in NSCs remains unclear. In this study, we investigated the role of p66Shc in NSC apoptosis by generating p66Shc knockout (p66KO) NSCs and assessing their responses to EGF withdrawal, EGFR inhibition, and MEK inhibition. We found that p66KO NSCs resisted apoptosis induced by EGF deprivation and EGFR-ERK pathway inhibition. In contrast, p66KO NSCs maintained their sensitivity to staurosporine, a general apoptosis inducer. Furthermore, p66KO NSCs subjected to prolonged MEK inhibition continued to differentiate into neurons, demonstrating their ability to evade apoptosis and progress through neuronal differentiation. These findings identify p66Shc as a pivotal regulator of NSC apoptosis in response to disrupted EGFR-ERK signalling. The ability of p66KO NSCs to resist apoptosis and differentiate without EGFR-ERK signalling highlights the potential of targeting p66Shc in conditions where growth factor signalling is disrupted, such as neurodegenerative diseases or brain injuries. Additionally, the role of p66Shc in modulating survival pathways may have broader implications for NSC-like cancers, where assessing p66Shc levels could provide prognostic value for the sensitivity of cancers to EGFR- or MEK-inhibition-based chemotherapies.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"479"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539119","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}

引用次数: 0

The cancer-associated SF3B1^K700E spliceosome mutation confers enhanced sensitivity to BV-6-induced cytotoxicity. 癌症相关的SF3B1K700E剪接体突变增强了对bv -6诱导的细胞毒性的敏感性。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07790-y

Lydia E Roets, Jaine K Blayney, Hayley P McMillan, Patrick J Preston, Alexander M Mutch, Ken I Mills, Kienan I Savage, Katrina M Lappin

{"title":"The cancer-associated SF3B1K700E spliceosome mutation confers enhanced sensitivity to BV-6-induced cytotoxicity.","authors":"Lydia E Roets, Jaine K Blayney, Hayley P McMillan, Patrick J Preston, Alexander M Mutch, Ken I Mills, Kienan I Savage, Katrina M Lappin","doi":"10.1038/s41419-025-07790-y","DOIUrl":"10.1038/s41419-025-07790-y","url":null,"abstract":"Recurrent somatic mutations in the key spliceosome component, SF3B1, have been identified at various frequencies across several cancer types. The most common hotspot mutation is the K700E missense mutation, and while its effects on splicing have been well characterised at the molecular level, the mis-spliced genes that contribute to cancer progression and/or dictate responses to therapy are still unclear. Here, we used we use cell line modelling to assess the impact of the SF3B1K700E mutation on the cellular response to various apoptosis-inducing agents. Our data suggest that the SF3B1K700E mutation leads to reduced cFLIP levels, along with defects in the splicing and translation of BCL2, causing a shift in the balance of pro- and anti-apoptotic genes and proteins, which confers greater sensitivity to the bivalent SMAC mimetic, BV-6. As such, BV-6 may represent a therapeutic opportunity for patients with SF3B1 mutant cancers.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"476"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539123","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}

引用次数: 0

Neuroprotection of photoreceptors by combined inhibition of both Fas and autophagy pathways in P23H mice. 联合抑制Fas和自噬途径对P23H小鼠光受体的神经保护作用。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07793-9

Mengling Yang, Jingyu Yao, Lin Jia, Andrew J Kocab, David N Zacks

{"title":"Neuroprotection of photoreceptors by combined inhibition of both Fas and autophagy pathways in P23H mice.","authors":"Mengling Yang, Jingyu Yao, Lin Jia, Andrew J Kocab, David N Zacks","doi":"10.1038/s41419-025-07793-9","DOIUrl":"10.1038/s41419-025-07793-9","url":null,"abstract":"The P23H variant of rhodopsin (RHO) is a common cause of autosomal dominant retinitis pigmentosa (adRP). Our previous data have shown that both the Fas (CD95) death receptor and hyperactivation of autophagy contribute to photoreceptor (PR) death in a mouse model of P23H-RHO adRP. Individually, inhibition of Fas or suppression of autophagy flux improves PR survival and function. The purpose of this study is to examine whether combined inhibition of Fas receptor activation and reducing autophagy flux would have an additive effect on PR survival and function in the P23H mouse. We crossed the Lpr mouse (which contains a functional knockout of the Fas receptor) with the P23H mouse to generate the Lpr/P23H mouse. Hydroxychloroquine (HCQ) was given in the drinking water at P21 to reduce autophagy flux. As an alternative to genetic inhibition of the Fas receptor, pharmacological blockade of the Fas receptor was achieved using intravitreal injections of the Fas inhibitor, ONL1204, administered via intravitreal injection at P14 and 2 months of age. Fellow eyes were injected with vehicle solution as controls. PR cell death, structure and function of the retina, as well as the activation of immune cells, were evaluated. Consistent with previous data, the Lpr/P23H mice exhibited a decreased rate of photoreceptor degeneration and reduced inflammation compared with P23H. Treatment of these mice with HCQ further preserved photoreceptor survival and function lowered the activation of immune cells, and resulted in reduced production of inflammatory cytokines in the retina. These results were recapitulated in HCQ-treated P23H mice receiving intravitreal injections of ONL1204. Our data suggest that in the mouse model of P23H adRD, inhibition of both the Fas pathway and autophagy pathways results in a greater protective effect, demonstrating the potential multipronged therapeutic approach to reduce PR death and improve retinal function in patients with P23H.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"469"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539117","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}

引用次数: 0

Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations. 目前对脓毒症的认识：机制、生理功能、在疾病中的作用、药理学应用和命名建议。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07784-w

Anton Tkachenko, Mohammad A Alfhili, Jawaher Alsughayyir, Alessandro Attanzio, Abdulla Al Mamun Bhuyan, Bożena Bukowska, Antonio Cilla, Martha A Quintanar-Escorza, Michael Föller, Ondrej Havranek, Kashif Jilani, Anatolii Onishchenko, Etheresia Pretorius, Volodymyr Prokopiuk, Ignazio Restivo, Luisa Tesoriere, Grazia Maria Virzì, Thomas Wieder

{"title":"Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations.","authors":"Anton Tkachenko, Mohammad A Alfhili, Jawaher Alsughayyir, Alessandro Attanzio, Abdulla Al Mamun Bhuyan, Bożena Bukowska, Antonio Cilla, Martha A Quintanar-Escorza, Michael Föller, Ondrej Havranek, Kashif Jilani, Anatolii Onishchenko, Etheresia Pretorius, Volodymyr Prokopiuk, Ignazio Restivo, Luisa Tesoriere, Grazia Maria Virzì, Thomas Wieder","doi":"10.1038/s41419-025-07784-w","DOIUrl":"10.1038/s41419-025-07784-w","url":null,"abstract":"Early studies have shown that erythrocytes have caspase-3 and caspase-8 and are capable of dying through an apoptotic-like cell death triggered by Ca2+ ionophores. This cell death is associated with apoptosis-like morphological signs, including cell shrinkage, membrane blebbing, and phosphatidylserine externalization. To emphasize that mature erythrocytes don't have the apoptotic mitochondrial machinery and distinguish this unique cell death modality from apoptosis, it was named \"eryptosis\". Over recent decades, our knowledge of eryptosis has been significantly expanded, providing more insights into the uniqueness of cell death pathways in erythrocytes. In this review, we aim to summarize our current understanding of eryptosis, formulate the nomenclature and guidelines to interpret results of eryptosis studies, provide a synopsis of morphological and biochemical features of eryptosis, and highlight the role of eryptosis in health and disease, including its druggability.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"467"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539110","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}

引用次数: 0

AK4 promotes nasopharyngeal carcinoma metastasis and chemoresistance by activating NLRP3 inflammatory complex. AK4通过激活NLRP3炎症复合体促进鼻咽癌转移和化疗耐药。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07805-8

Sai-Lan Liu, Li Yuan, Xue-Song Sun, Bei-Bei Xiao, Kai-Qi Lan, Zi-Jian Lu, Da-Feng Lin, Xiao-Yun Li, Jin-Jie Yan, Shu-Mei Yan, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai

{"title":"AK4 promotes nasopharyngeal carcinoma metastasis and chemoresistance by activating NLRP3 inflammatory complex.","authors":"Sai-Lan Liu, Li Yuan, Xue-Song Sun, Bei-Bei Xiao, Kai-Qi Lan, Zi-Jian Lu, Da-Feng Lin, Xiao-Yun Li, Jin-Jie Yan, Shu-Mei Yan, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai","doi":"10.1038/s41419-025-07805-8","DOIUrl":"10.1038/s41419-025-07805-8","url":null,"abstract":"Metastasis is the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Our previous study developed a transcriptomics-based gene signature (AK4, CPAMD8, DDAH1, and CRTR1) to predict metastasis in NPC and identify candidates that could benefit from induction chemotherapy (IC). Of these, adenylate kinase 4 (AK4) is a potent oncogene involved in the malignant progression of a variety of tumors. This study investigated the expression and mechanism of action of AK4, a member of the AK family of enzymes, in NPC. Quantitative real-time PCR, western blotting, and immunohistochemistry revealed that AK4 was upregulated in NPC and correlated with metastasis and chemoresistance. Stable ectopic overexpression of AK4 in NPC cell lines conferred resistance to taxol-induced apoptosis, promoted the migration, invasion, and EMT phenotype, and induced IL-1β secretion by activating the NLRP3 signaling pathway; knockdown of AK4 had the opposite effects. Mechanistically, AK4 co-localized with NNT, upregulated NLRP3 and IL-1β, and consequently altered NPC cell metastasis and chemoresistance. AK4 may play a role in the development of NPC and represent a potential therapeutic target.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"480"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539109","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}

引用次数: 0

Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction. n-乙酰转移酶10对巨噬细胞活化和炎症性心功能障碍的影响。

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-07-01 DOI: 10.1038/s41419-025-07796-6

Zilong Xiao, Xiang Wei, Peng Li, Ruizhen Chen, Ziqing Yu, Yixiu Liang, Yangang Su, Junbo Ge

{"title":"Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction.","authors":"Zilong Xiao, Xiang Wei, Peng Li, Ruizhen Chen, Ziqing Yu, Yixiu Liang, Yangang Su, Junbo Ge","doi":"10.1038/s41419-025-07796-6","DOIUrl":"10.1038/s41419-025-07796-6","url":null,"abstract":"Inflammation-induced cardiac dysfunction, driven by an abnormal immune response, significantly contributes to sepsis-related mortality. Controlling excessive pro-inflammatory cytokine production by immune cells remains a significant challenge. This study investigated the role of N-acetyltransferase 10 (NAT10) in macrophage activation and its contribution to inflammation-induced cardiac dysfunction. Using bone marrow-derived macrophages and an endotoxemia mouse model, we found that NAT10 is significantly upregulated in response to lipopolysaccharide (LPS) due to the deubiquitinating enzyme USP39, which stabilizes the NAT10 protein. ac4C RNA sequencing identified ETS2 as a direct target of NAT10, where the ac4C modification enhanced ETS2 mRNA stability and translation, promoting a pro-inflammatory phenotype in macrophages. NAT10 deficiency reduces LPS-induced macrophage activation and cytokine production, improving cardiac function in mice. Pharmacological inhibition of NAT10 using remodelin produced similar protective effects. Our findings reveal a novel post-transcriptional pathway and highlight the therapeutic potential of targeting NAT10 to mitigate inflammation-induced cardiac injury in endotoxemia.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"471"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539112","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}

引用次数: 0