Cell Death & Disease最新文献

{"title":"RelB/ILF2-GM-CSF loop sustains tumor-MDSC communication in prostate cancer immunosuppression.","authors":"Fan Xu, Min Li, Yuan Zhang, Zhi Xu, Qiming Yin, Sijia Zhang, Fei Wu, Yuyan Ma, Zhangjun Jia, Xiumei Wang, Jiachen Dong, Ziyu Zhou, Jian Jian Li, Xiao Li, Yanyan Zhang","doi":"10.1038/s41419-026-09098-x","DOIUrl":"10.1038/s41419-026-09098-x","url":null,"abstract":"<p><p>Prostate cancer (PCa) exhibits an immune \"cold\" tumor microenvironment (TME) with significant enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs), which contribute to tumor progression and poor responses to immune checkpoint blockade (ICB). Although extensively studied, the precise mechanism underlying the tumor-intrinsic signals that educate and sustain the expansion and immunosuppressive function of MDSCs remains unelucidated. Here, we identify a previously unrecognized function of RelB by which nuclear interaction with ILF2 restricts ubiquitin-mediated degradation and sustains nuclear stability of RelB, thereby enhancing RelB-mediated CSF2 transactivation and enhanced GM-CSF (granulocyte-macrophage colony-stimulating factor) production and secretion. The secreted GM-CSF, in turn, promotes RelB nuclear accumulation, forming a feed-forward loop for sustaining GM-CSF generation. In MDSCs, GM-CSF activates STAT3-mediated MDSC expansion and immunosuppression. Disruption of RelB/ILF2 complex attenuates GM-CSF-driven MDSC expansion, restores CD8⁺ T cell-mediated antitumor activity, and inhibits tumor growth. In addition, a RelB-targeting peptide SN52 sensitizes PCa tumors to PD-1 blockade therapy. Collectively, our findings identify the RelB/ILF2-GM-CSF loop as a central regulator of MDSC-mediated immunosuppression, which may be targeted to improve PCa response to ICB.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419071","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":"K-Ras controls asymmetric cell divisions from the primary cilium.","authors":"Rohan Chippalkatti, Elisabeth Schaffner-Reckinger, Anthoula Gaigneaux, Bianca Parisi, Sara Bottone, Christina Laurini, Yashar Rouzbahani, Mariska Dijkers, Atanasio Gómez-Mulas, Thomas Sauter, Jeroen den Hertog, Christian Eggeling, Daniel Kwaku Abankwa","doi":"10.1038/s41419-026-09089-y","DOIUrl":"10.1038/s41419-026-09089-y","url":null,"abstract":"<p><p>The Ras-MAPK pathway drives central cellular processes, including cell proliferation and differentiation. How exactly Ras controls differentiation is however not understood. Supported by mathematical modeling and single-cell RNA sequencing we show that K-Ras4B sustains ciliation during differentiation thus restricting commitment of skeletal muscle stem and progenitor cells during asymmetric cell divisions. Modulation of K-Ras4B abundance or expression of oncogenic K-Ras4B-G12C perturb normal differentiation. K-Ras4B, but not N-Ras and H-Ras, localizes to the primary cilium and its abundance there depends on the ciliary trafficking chaperone PDE6D. The presence of B-Raf and active MEK at the base of and active ERK inside the cilium suggests that K-Ras4B is active there. Conditions that localize a K-Ras4B mutant only to the cilium are sufficient to sustain ciliation and normal differentiation. Finally, in vivo modulation of K-Ras4B activity during zebrafish embryogenesis perturbs ciliation-dependent heart-looping. Our results thus imply a novel fundamental role of K-Ras4B in controlling ciliation and differentiation and suggest an explanation for the phenotypic similarities between RASopathies and ciliopathies.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418963","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":"Role of the trophoblastic BMP7-TGM2 axis in the pathogenesis and prevention of preeclampsia.","authors":"Qiaoqiao Ding, Mingxi Liu, Binbin Zhao, Yaxin Su, Ying Zhong, Cameron Klein, Junhao Yan, Peter C K Leung, Zi-Jiang Chen, Daimin Wei, Yan Li","doi":"10.1038/s41419-026-09111-3","DOIUrl":"10.1038/s41419-026-09111-3","url":null,"abstract":"<p><p>Preeclampsia (PE) is a major hypertensive disorder of pregnancy and a leading cause of maternal and perinatal mortality and morbidity worldwide. Aberrant placental development, characterized by shallow trophoblast invasion and incomplete remodeling of maternal spiral arteries, remains central to PE pathogenesis. In PE, tissue transglutaminase (TGM2) is dysregulated in the placenta, contributing to vascular dysfunction, inflammation, and impaired trophoblast differentiation, yet the upstream regulatory signals remain unknown. Bone morphogenetic protein 7 (BMP7) is abundantly expressed at the maternal-fetal interface and implicated in vascular homeostasis, but its role in regulating trophoblast function, especially related to PE pathogenesis, remains undefined. Here, single-cell transcriptomic profiling of placental tissues revealed coordinated downregulation of BMP7 and upregulation of TGM2 in PE relative to normotensive controls. Functional assays in immortalized and primary human trophoblasts demonstrated that BMP7 promotes trophoblast migration and invasion by suppressing TGM2 expression through the ALK2/3-SMAD1/5/9-SMAD4 pathway. Trophoblast organoid models further demonstrated the anti-invasive role of TGM2 in trophoblast differentiation during early placentation. In vivo, an adenovirus-expressing sFlt-1 (Ad sFlt-1)-induced PE mouse model showed increased placental Tgm2 expression, while recombinant BMP7 administration ameliorated PE-like symptoms. Although the protective effects of BMP7 in vivo are likely mediated by mechanisms beyond TGM2 alone, together these findings identify the BMP7-TGM2 axis as an important trophoblast-regulatory mechanism in PE and support BMP7 as a potential therapeutic candidate.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419098","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":"ENO2 sustains cancer stemness and metastatic competence through a phosphoenolpyruvate-dependent metabolic axis in triple-negative breast cancer.","authors":"Cing-Hong Wang, Ru-Tsun Mai, Ke Jia Khoo, Chi-Feng Hung, Cheng-Kuang Yang, Meng-Ju Wu, Chi-Hong Chao","doi":"10.1038/s41419-026-09106-0","DOIUrl":"10.1038/s41419-026-09106-0","url":null,"abstract":"<p><p>Enolase 2 (ENO2) is a neuron-specific glycolytic enzyme whose expression is elevated in aggressive breast cancers, yet its enzymatic and biological contributions to triple-negative breast cancer (TNBC) progression remain incompletely defined. Here, we demonstrate that ENO2 sustains cancer stem cell (CSC) properties and metastatic competence through a phosphoenolpyruvate (PEP)-dependent metabolic axis. Elevated ENO2 expression correlated with advanced tumor grade and poor clinical outcomes in TNBC cohorts, underscoring its clinical relevance. Genetic depletion of ENO2 impaired aerobic glycolysis and oxidative phosphorylation, reduced migration, invasion, and CSC frequency, and suppressed tumor growth and pulmonary metastasis in orthotopic models. Mechanistically, exogenous PEP or pyruvate restored CSC-associated traits and invasiveness in ENO2-deficient cells, supporting the functional involvement of ENO2-derived metabolites in CSC maintenance. Reconstitution with wild-type ENO2, but not a catalytically impaired mutant, restored CSC properties, invasiveness, and metastatic colonization, establishing that ENO2 catalytic activity is required for these malignant traits. Further analysis revealed that PKM2 perturbation preferentially attenuated PEP-mediated rescue while largely sparing pyruvate-mediated rescue, supporting a functional PEP-PKM2-pyruvate axis in CSC regulation. Consistently, PKM2 depletion partially blunted ENO2-mediated rescue; however, residual rescue despite PKM2 perturbation suggested additional PKM2-independent PEP-responsive mechanisms. Importantly, pharmacological inhibition of enolase with POMHEX phenocopied genetic ENO2 loss and suppressed CSC maintenance in vitro and tumor growth in vivo. Taken together, these findings identify the ENO2-driven PEP-dependent metabolic axis as a mechanistic link between metabolic reprogramming, cancer stemness, and metastasis, revealing a therapeutically actionable metabolic vulnerability in TNBC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419143","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":"Host heterogeneity shapes clonal selection and organotropism in an extranodal lymphoma mouse model.","authors":"Xiaoxi Li, Minyao Deng, Yong Jiang, Lingli Luo, Chenxiao Zhang, Hua Tang, Zhuang Wei, Jiayan Leng, Chuan Liu","doi":"10.1038/s41419-026-09014-3","DOIUrl":"10.1038/s41419-026-09014-3","url":null,"abstract":"<p><p>Tumor metastasis is a leading cause of patient mortality, with tumor dissemination and organotropism representing critical yet complex aspects of tumor biology that involve clonal selection and evolutionary dynamics. Current experimental models inadequately recapitulate the spatiotemporal dissemination and phenotypic heterogeneity of human cancers, highlighting a critical need for more physiologically relevant preclinical platforms. In this study, we utilized a kidney-tropic primary extranodal lymphoma model to explore the role of EFNB1 in lymphoma dissemination across two distinct mouse strains, C57BL/6J and C57BL/10J. Intriguingly, EFNB1-overexpressing lymphoma cells displayed markedly different progression rates and colonization patterns in these strains. EFNB1-null and EFNB1-high lymphomas derived from the two strains underwent distinct clonal selection and exhibited significant transcriptomic heterogeneity, including RNA base substitutions, as well as differential expression of nuclear histone genes and mitochondrial respiratory chain genes. Notably, clonal origin alone did not determine lymphoma organotropism. Collectively, this study establishes a readily reproducible extranodal lymphoma model and demonstrates that host heterogeneity can reshape transcriptional heterogeneity, drive tumor clonal selection, and ultimately dictate organotropism. These findings suggest that host heterogeneity may serve as a valuable prognostic indicator for lymphoma.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418949","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":"MND1 regulates PANoptosis and stemness of lung adenocarcinoma cells by stabilizing RCOR2 mRNA.","authors":"Lianlian Ouyang, Xingjie Tang, Shiyao Jiang, Yating Liu, Na Liu, Chao Mao, Yuanbing Chen, Ye Fan, Ziyun Zhang, Jingjing Huang, Yongguang Tao, Xing Yu, Li Cong, Yiqun Jiang","doi":"10.1038/s41419-026-09012-5","DOIUrl":"10.1038/s41419-026-09012-5","url":null,"abstract":"<p><p>PANoptosis is an inflammatory programmed cell death mechanism that depends on the PANoptosome complex, which integrates hallmark features of apoptosis, necroptosis, and pyroptosis. Meiotic nuclear division protein 1 (MND1), a meiosis-specific protein, primarily participates in homologous chromosome pairing and DNA double-strand break repair. However, the precise role of MND1 in regulating PANoptosis and tumor stemness remains unclear. Here, we provide evidence that MND1 participates in the regulatory mechanisms of PANoptosis and cell stemness in lung adenocarcinoma (LUAD). Mechanistically, MND1 recruits PABPC1 to interact with the 3'-UTR of RCOR2 mRNA, significantly enhancing its stability. As a crucial component of the pluripotency regulatory network, the stable expression of RCOR2 is essential for maintaining tumor cell stemness. Our findings suggest MND1 acts as an oncogene in LUAD by stabilizing RCOR2 mRNA, maintaining the stemness of LUAD and inhibiting PANoptosis. Notably, this study represents the first investigation to elucidate the regulatory role of MND1 in modulating both stemness properties and PANoptosis in LUAD, providing valuable insights into the molecular mechanisms underlying LUAD pathogenesis.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418954","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":"CXCR2 blockade potentiates HDAC3 deletion mediated antitumor immunity in colorectal cancer.","authors":"Yukun Zhang, Yeping Yu, Fang Yang, ZiHeng Zhao, Xiaodong Gu, Zhenyang Li, Yiming Zhou, Wenqian Zhang, Huichun Chen, Jianbin Xiang","doi":"10.1038/s41419-026-09006-3","DOIUrl":"10.1038/s41419-026-09006-3","url":null,"abstract":"<p><p>HDAC3 is highly expressed in colorectal cancer (CRC) and associated with poor prognosis. This study reveals that HDAC3 deletion dually regulates chemokine expression through epigenetic mechanisms, promoting CD8⁺ T cell infiltration (via CXCL10) on one hand, while enhancing the recruitment of myeloid-derived suppressor cells (MDSCs) (via CXCL1/2/3/5) on the other. The latter, mediated through CXCR2 signaling, counteracts the intrinsic anti-tumor effect of HDAC3 deletion. We further demonstrate that combining a CXCR2 inhibitor effectively blocks MDSC infiltration and significantly enhances the immunotherapeutic efficacy mediated by HDAC3 deletion. This study systematically elucidates the \"double-edged sword\" role of HDAC3 in the CRC immune microenvironment and provides a theoretical and experimental basis for an HDAC3/CXCR2 dual-targeting therapeutic strategy.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419170","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":"Oocyte-specific knockout of eIF2B subunits causes apoptosis of mouse oocytes within the early growing follicles via DNA damage and mitochondrial dysfunction.","authors":"Weiyong Wang, Huiyu Liu, Biao Li, Shuang Liu, Luchun Zhang, Ying Wei, Hongwei Wei, Xiaodan Zhang, Xiaoqiong Hao, Meijia Zhang","doi":"10.1038/s41419-026-09092-3","DOIUrl":"10.1038/s41419-026-09092-3","url":null,"abstract":"<p><p>Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI). In this study, we demonstrated that the conditional knockout of eukaryotic translation initiation factor 2B (eIF2B) subunits Eif2b2, Eif2b3, Eif2b4 or Eif2b5, but not Eif2b1, in mouse oocytes of primordial follicles caused oocyte apoptosis within the early growing follicles. Integrative Ribo-seq and RNA-seq analysis revealed the upregulation of integrated stress response- and DNA damage-related genes, and the downregulation of oocyte development-related genes in Eif2b4-cKO oocytes. Then, further research indicated that the depletion of Eif2b4 in oocytes resulted in mitochondrial dysfunctions characterized by decreased mitochondrial membrane potential, mtDNA copy numbers, and ATP content, along with excessive accumulation of reactive oxygen species (ROS). At the same time, the depletion of Eif2b4 in oocytes resulted in the increased levels of DNA damage response (DDR) proteins (NBS1, p-ATM, p-CHK2, and p53) and proapoptotic protein BAX, as well as the decreased levels of DNA damage repair protein Polβ and anti-apoptotic protein BCL-xL. Collectively, these findings indicate that the depletion of eIF2B subunits in mouse oocytes leads to oocyte apoptosis within the early growing follicles by DNA damage and mitochondrial dysfunction. This study provides new insights into the pathogenesis and genetic diagnosis of POI.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419097","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":"NKD1 promotes the progression and 5-FU resistance of colorectal cancer via the Wnt/β-catenin signaling.","authors":"Lingyi Dong, Zhangquan Yang, Zelin Xu, Guotao Huang, Xuesi Yang, You Lv, Kunzhai Huang, Zhaohui Liu, Fuxing Zhang, Kewei Jiang, Zhilong Yu","doi":"10.1038/s41419-026-09077-2","DOIUrl":"10.1038/s41419-026-09077-2","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) resistance continues to pose a considerable barrier in the postoperative management of advanced colorectal cancer (CRC). This study identified Naked cuticle homolog 1 (NKD1) as a key factor associated with 5-FU resistance in CRC based on sequencing data from the GEO and TCGA databases. Elevated NKD1 expression correlated with adverse clinicopathological features and poor patient survival. Functional assays revealed that NKD1 overexpression elevated the IC50 of 5-FU, promoted tumor cell proliferation, and attenuated apoptosis in both drug-treated and untreated settings. Additionally, NKD1 promoted CRC cell migration and invasion, regulated tumor stem cell markers. Mechanistically, NKD1 stabilizes DVL protein, regulates APC and FZD7, and fosters nuclear accumulation of β-catenin, initiating transcriptional programs downstream of Wnt signaling. Silencing NKD1 synergized with 5-FU to improve therapeutic efficacy in patient-derived organoid and xenograft models. These results establish NKD1 as a key regulator of CRC malignancy and chemoresistance via Wnt/β-catenin pathway activation, supporting its potential as a dual biomarker and therapeutic target in combination regimens.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419026","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":"Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.","authors":"David Soriano-Castell, Marie Goujon, Nawab John Dar, Antonio Currais, Pamela Maher","doi":"10.1038/s41419-026-09108-y","DOIUrl":"10.1038/s41419-026-09108-y","url":null,"abstract":"<p><p>Cellular senescence, a complex biological process characterized by irreversible cell cycle arrest and the senescence-associated secretory phenotype, has emerged as a critical target for therapeutic development for age-related diseases. Ferroptosis, an iron-dependent regulated cell death pathway driven by the accumulation of lipid peroxidation in cell membranes, has been implicated in age-related disorders. This study investigated the relationship between cellular senescence and ferroptosis. Using human fetal lung WI-38 fibroblasts induced to senesce via replicative exhaustion, we report a novel role for acid ceramidase (ACase), which breaks down ceramides into sphingosine and free fatty acids, in regulating the sensitivity of senescent cells to RSL3-induced lipid peroxidation and ferroptosis through the modulation of polyunsaturated fatty acid composition of membrane phospholipids. Furthermore, we demonstrate a cell non-autonomous paracrine sensitization of non-senescent cells to ferroptosis by senescent cells. Together, these findings unveil ACase as a novel regulator of the ferroptosis pathway and open promising therapeutic avenues for targeting senescence-linked disorders and advancing healthy aging strategies.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419164","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}