Cell Death Discovery最新文献_第7页

Gasdermin E in glioblastoma -pyroptosis resistance and tumor-promoting functions. 胶质母细胞瘤抗焦亡及促瘤功能中的气真皮蛋白E。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-21 DOI: 10.1038/s41420-025-02572-z

Ege Solel, Egil Brudvik, Lars Andreas Rømo Ystaas, Yahaya A Yabo, Emma Rigg, Romi Roy Choudhury, Halala Sdik Saed, Dieter Henrik Heiland, Rolf Bjerkvig, Jubayer Hossain, Hrvoje Miletic

{"title":"Gasdermin E in glioblastoma -pyroptosis resistance and tumor-promoting functions.","authors":"Ege Solel, Egil Brudvik, Lars Andreas Rømo Ystaas, Yahaya A Yabo, Emma Rigg, Romi Roy Choudhury, Halala Sdik Saed, Dieter Henrik Heiland, Rolf Bjerkvig, Jubayer Hossain, Hrvoje Miletic","doi":"10.1038/s41420-025-02572-z","DOIUrl":"10.1038/s41420-025-02572-z","url":null,"abstract":"Treatment of glioblastoma (GB), the most common and most aggressive malignant brain tumor, has made little progress over the past two decades. Despite extensive research on apoptosis and autophagy, necrotic cell death mechanisms like pyroptosis, which have the potential to stimulate anti-tumor immune responses, remain largely underexplored in GB. Here, we investigated whether Gasdermin E (GSDME)-mediated pyroptosis can be induced in GB by employing the drug raptinal, an inducer of cytochrome c release. Using human patient-derived and mouse GB cell lines, we showed that raptinal promotes GSMDE cleavage. However, although a strong pyroptotic response was observed in mouse cell lines, it was weak in human cell lines. This resistance was partially reversed by the calcium chelator BAPTA-AM, indicating that membrane repair mechanisms may counteract the pyroptotic response. Gsdme knockout (KO) in mouse GB cells unexpectedly prolonged the survival of immunocompetent mice, demonstrating a tumor-promoting role of GSDME independent of its pyroptotic function. Analysis of the immune microenvironment revealed that Gsdme KO promoted infiltration of T cells, which was confirmed by spatial transcriptomic analysis of GB patient samples. In addition, Gsdme/GSMDE KO reduced the invasive capacity of mouse/human GB cells. In conclusion, active membrane repair mechanisms may impair the pyroptotic efficacy in GB. GSDME has a tumor-promoting role in GB by suppressing T cell infiltration and increasing tumor cell invasion.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"284"},"PeriodicalIF":6.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac. 截断的LKB1通过替代Smac非酶促fas诱导的细胞凋亡。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-21 DOI: 10.1038/s41420-025-02570-1

Yutaro Yamada, Mei Tsuchida, Takuya Noguchi, Takumi Yokosawa, Maki Mitsuya, Tatsuya Shimada, Daisuke Oikawa, Yusuke Hirata, Fuminori Tokunaga, Pascal Schneider, Atsushi Matsuzawa

{"title":"Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac.","authors":"Yutaro Yamada, Mei Tsuchida, Takuya Noguchi, Takumi Yokosawa, Maki Mitsuya, Tatsuya Shimada, Daisuke Oikawa, Yusuke Hirata, Fuminori Tokunaga, Pascal Schneider, Atsushi Matsuzawa","doi":"10.1038/s41420-025-02570-1","DOIUrl":"10.1038/s41420-025-02570-1","url":null,"abstract":"Although liver kinase B1 (LKB1) has been established as a tumor suppressor kinase, its mechanism of action is incompletely understood. Here we describe a novel nonenzymatic function of LKB1 in cell death induced by Fas/CD95. In BID knockout HeLa cells, inactivation of mitochondrial outer membrane permeabilization (MOMP) prevents Smac-induced inhibition of X-linked inhibitor of apoptosis (XIAP), causing resistance to Fas-induced apoptosis. However, reexpression of LKB1 in those cells naturally deficient for endogenous LKB1 restored apoptosis. Mechanistically, caspase-8 activated by Fas processed LKB1 to a truncated form, tLKB1. Both WT and kinase-inactive LKB1 antagonized XIAP to restore apoptosis, but somatic mutants of LKB1 found in Peutz-Jeghers syndrome (PJS) failed to do so. Thus, in addition to the known caspase-8 / tBid / Smac / XIAP pro-apoptotic axis, our results unveil a novel one, caspase-8 / tLKB1 / XIAP that potentially contributes to the antitumor functions of LKB1.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"285"},"PeriodicalIF":6.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Nrf2-HMOX1 pathway as a therapeutic target for reversing cisplatin resistance in non-small cell lung cancer via inhibiting ferroptosis. Nrf2-HMOX1途径通过抑制铁下垂逆转非小细胞肺癌顺铂耐药的治疗靶点

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-21 DOI: 10.1038/s41420-025-02564-z

Ling Zuo, Xinru Zou, Jia Ge, Shuning Hu, Yixuan Fang, Yi Xu, Rui Chen, Sheng Xu, Guangyang Yu, Xiaorong Zhou, Lili Ji

{"title":"The Nrf2-HMOX1 pathway as a therapeutic target for reversing cisplatin resistance in non-small cell lung cancer via inhibiting ferroptosis.","authors":"Ling Zuo, Xinru Zou, Jia Ge, Shuning Hu, Yixuan Fang, Yi Xu, Rui Chen, Sheng Xu, Guangyang Yu, Xiaorong Zhou, Lili Ji","doi":"10.1038/s41420-025-02564-z","DOIUrl":"10.1038/s41420-025-02564-z","url":null,"abstract":"Cisplatin resistance is a major cause of poor prognosis in non-small cell lung cancer (NSCLC). Cisplatin-induced lung cancer cell death is associated with ferroptosis, a type of recently identified programmed cell death. Nrf2 is a critical component of the antioxidant system, and its protumorigenic activity in lung cancer has been extensively studied. However, the role of Nrf2 in cisplatin-induced ferroptosis and drug resistance remains elusive. Here, we demonstrated that cisplatin treatment induced ferroptosis in parental A549 lung adenocarcinoma cells and that this effect was significantly reduced in cisplatin-resistant A549/DDP cells. Knocking down Nrf2-sensitized A549/DDP cells to cisplatin-induced cytotoxicity by enhancing ferroptosis. Moreover, we demonstrated that Nrf2 promotes the expression of HMOX1 and that the Nrf2-HMOX1 pathway is critical for mediating its anti-ferroptotic function. Additionally, immunohistochemical analysis of NSCLC specimens revealed that Nrf2 expression was correlated with HMOX1 and high levels of Nrf2 and HMOX1 were associated with poor patient survival. These findings suggest that the HMOX1-Nrf2 pathway significantly influences treatment outcomes in NSCLC. Ultimately, we demonstrated that treatment with the Nrf2 inhibitor ML385 promoted ferroptosis by inhibiting the Nrf2-HMOX1 pathway, restoring cisplatin sensitivity in drug-resistant cells. Our findings provide insights into the mechanism underlying cisplatin resistance and suggest that targeting the Nrf2-HMOX1 pathway enhances cisplatin-induced ferroptosis and improves NSCLC treatment outcomes.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"287"},"PeriodicalIF":6.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ferroptosis in periodontitis: mechanisms, impacts, and systemic connections. 牙周炎中的上铁下垂：机制、影响和系统联系。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-20 DOI: 10.1038/s41420-025-02550-5

Peng Guan, Qijun Ruan, Jiatong Li, Mengying Xi, Weijuan Qi, Kang I Ko, Jia Ni

引用次数: 0

Colorectal cancer cell line-derived organoid model with stem cell properties captures the regrowing state of residual cancer cells after neoadjuvant chemotherapy. 具有干细胞特性的结直肠癌细胞系衍生的类器官模型捕捉了新辅助化疗后残余癌细胞的再生状态。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-20 DOI: 10.1038/s41420-025-02567-w

Kiyotaka Nakano, Eiji Oki, Masaki Yamazaki, Masami Suzuki, Shigeto Kawai, Takanori Fujita, Atsuhiko Kato, Yoko Zaitsu, Tomoko Jogo, Chie Kato, Takeshi Watanabe, Eri Hashimoto, Chiyoko Nishime, Etsuko Fujii, Koji Ando, Genta Nagae, Norifumi Harimoto, Mitsuhiko Ota, Hiroshi Saeki, Hiroyuki Aburatani, Yoshihiko Maehara, Tatsumi Yamazaki

{"title":"Colorectal cancer cell line-derived organoid model with stem cell properties captures the regrowing state of residual cancer cells after neoadjuvant chemotherapy.","authors":"Kiyotaka Nakano, Eiji Oki, Masaki Yamazaki, Masami Suzuki, Shigeto Kawai, Takanori Fujita, Atsuhiko Kato, Yoko Zaitsu, Tomoko Jogo, Chie Kato, Takeshi Watanabe, Eri Hashimoto, Chiyoko Nishime, Etsuko Fujii, Koji Ando, Genta Nagae, Norifumi Harimoto, Mitsuhiko Ota, Hiroshi Saeki, Hiroyuki Aburatani, Yoshihiko Maehara, Tatsumi Yamazaki","doi":"10.1038/s41420-025-02567-w","DOIUrl":"10.1038/s41420-025-02567-w","url":null,"abstract":"The effectiveness of colorectal cancer (CRC) therapy is limited owing to the absence of treatments targeting drug-tolerant residual cancer cells. Although neoadjuvant therapy is effective, pathological examination of residual tumors has revealed the presence of small clusters of LGR5-positive cancer cells in the fibrous tissue. Here, we established a colorectal cancer cell line-derived organoid (CCD-organoid) regrowth model using a patient-derived cell line with cancer stem cell properties and demonstrated that it displayed the morphological characteristics of small clusters in clinical tissues. Time course analysis of single-cell RNA sequencing of the CCD-organoid regrowth model revealed various states and dynamic alterations within non-cycling cells. We identified subpopulations highly expressing protein translation-related genes RPL17 and EEF1G. To identify key signals for the transition of residual cancer cells to regrowth, we evaluated inhibitors targeting pathways such as the Wnt pathway, reactive oxygen species pathway, and RNA polymerase I pathway, highlighted in the single-cell RNA sequencing analysis. Only the polymerase I-inhibitor BMH-21 significantly reduced tumor growth both in vitro and in vivo, indicating the critical cell subpopulation driving recurrence. Our results demonstrate the possibility of a unique therapeutic target for CRC treatment targeting drug-tolerant residual cancer cells.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"282"},"PeriodicalIF":6.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death. 杀伤NAFLD/NASH阶段的肝细胞癌：靶向调节细胞死亡的综合视角

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-19 DOI: 10.1038/s41420-025-02558-x

Jianxin Xi, Shuangyin Lei, Jie Chen, Jiahui Liu, Chenhao Shan, Xun Sun, Qianqian Zheng, Xiaoju Shi

{"title":"Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.","authors":"Jianxin Xi, Shuangyin Lei, Jie Chen, Jiahui Liu, Chenhao Shan, Xun Sun, Qianqian Zheng, Xiaoju Shi","doi":"10.1038/s41420-025-02558-x","DOIUrl":"10.1038/s41420-025-02558-x","url":null,"abstract":"Nonalcoholic steatohepatitis (NASH) has been identified as a significant risk factor contributing to the rising incidence of hepatocellular carcinoma (HCC). With the evolving epidemiological characteristics of NASH, the incidence of NASH-related HCC has increased substantially. Recent advances in the study of regulated cell death (RCD) mechanisms have uncovered their roles in the pathogenesis of NAFLD/NASH and associated HCC, offering novel insights and directions for targeted therapeutic strategies. Although numerous studies have highlighted the critical role of RCD mechanisms in NAFLD/NASH and related HCC, significant challenges remain in developing effective targeted therapies and translating them into clinical applications. This review aims to summarize the current progress in understanding the role of RCD in NAFLD/NASH and associated HCC, explore potential therapeutic strategies and clinical applications, and provide new perspectives and therapeutic targets for treating NAFLD/NASH. Ultimately, the goal is to control disease progression at the NAFLD/NASH stage and prevent its progression to HCC.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"281"},"PeriodicalIF":6.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 role of MBD2 in immune cell development, function, and autoimmune diseases. MBD2在免疫细胞发育、功能和自身免疫性疾病中的作用。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-19 DOI: 10.1038/s41420-025-02563-0

Yunfei Zhang, Yufeng Fan, Ying Hu, Xiaocui Wang, Bin Wen, Xuemei Duan, Haonan Li, Shumin Dong, Ze Yan, Weiwei Zhang, Yukai Jing

{"title":"The role of MBD2 in immune cell development, function, and autoimmune diseases.","authors":"Yunfei Zhang, Yufeng Fan, Ying Hu, Xiaocui Wang, Bin Wen, Xuemei Duan, Haonan Li, Shumin Dong, Ze Yan, Weiwei Zhang, Yukai Jing","doi":"10.1038/s41420-025-02563-0","DOIUrl":"10.1038/s41420-025-02563-0","url":null,"abstract":"DNA methylation is a key epigenetic modification that regulates gene expression, cell differentiation, and genome stability. Aberrant DNA methylation patterns, including the hypermethylation or global hypomethylation of tumor suppressor genes, are strongly associated with various human diseases, such as cancer, autoimmune disorders, and metabolic syndrome. DNA methylation predominantly occurs at CpG dinucleotides, influencing transcription by altering chromatin structure and accessibility. MBD2 (Methyl-CpG-binding proteins 2) play a crucial role in interpreting these epigenetic marks and regulating downstream gene expression. In disease contexts, aberrant DNA methylation disrupts cellular homeostasis by silencing key regulatory genes or activating pathological pathways. Current research primarily focuses on MBD2 in cancer, with less emphasis on its role in autoimmune diseases. This review discusses the role of MBD2 in regulating immune cell development and differentiation through epigenetic mechanisms, particularly DNA methylation and its regulatory components. Furthermore, it highlights the mechanistic contributions of MBD2 to autoimmune diseases such as systemic lupus erythematosus and evaluates its potential as a novel therapeutic target for these conditions.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"280"},"PeriodicalIF":6.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Roles of ACSL4/GPX4 and FSP1 in oxalate-induced acute kidney injury. ACSL4/GPX4和FSP1在草酸诱导的急性肾损伤中的作用

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-17 DOI: 10.1038/s41420-025-02557-y

Keng Ye, Ruilong Lan, Zhimin Chen, Kunmei Lai, Yankun Song, Guoping Li, Huabin Ma, Hong Chen, Yanfang Xu

{"title":"Roles of ACSL4/GPX4 and FSP1 in oxalate-induced acute kidney injury.","authors":"Keng Ye, Ruilong Lan, Zhimin Chen, Kunmei Lai, Yankun Song, Guoping Li, Huabin Ma, Hong Chen, Yanfang Xu","doi":"10.1038/s41420-025-02557-y","DOIUrl":"10.1038/s41420-025-02557-y","url":null,"abstract":"Ferroptosis has emerged as a crucial driver of injury in various organs, including acute kidney injury (AKI). However, the regulatory roles and underlying mechanisms of key genes involved in ferroptosis during oxalate-induced AKI are not fully understood. In this study, we conducted single-cell RNA sequencing (scRNA-seq) analysis of kidney samples, revealing the occurrence of ferroptosis in renal tubular cells of an oxalate-induced AKI mouse model, which was confirmed in subsequent in vitro experiments. Furthermore, renal tubule-specific deficiency of Acsl4 conferred significant protection against oxalate-induced AKI, as evidenced by alleviated structural and functional renal damage, reduced oxidative stress and decreased inflammatory cell infiltration, all of which collectively contribute to a reduction in ferroptosis. In contrast, Fsp1 deficiency exacerbated these pathological processes. Consistent with the in vivo findings, Acsl4 knockout in mouse renal tubular epithelial cell lines (MTECs) resulted in decreased lipid peroxidation and mitigation of mitochondrial dysfunction, thus reducing calcium oxalate (CaOX)-induced ferroptosis. Conversely, Fsp1 knockout in MTECs had the opposite effects. In addition, as expected, overexpression of the ferroptosis inhibitors GPX4 or FSP1 in MTECs significantly reduced CaOX-induced lipid peroxidation and cell ferroptosis. In summary, these findings indicated that oxalate exposure upregulated ferroptosis driver ACSL4 and downregulated inhibitors like GPX4 and FSP1, leading to lipid peroxidation and mitochondrial dysfunction, which collectively triggered ferroptosis in renal tubular cells. Modulating ACSL4/GPX4 and FSP1 axes presents a promising therapeutic strategy for oxalate-induced AKI.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"279"},"PeriodicalIF":6.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Neocarzilin A induces apoptosis and mitochondrial disturbance by targeting reticulon 4-mediated endoplasmic reticulum stress. Neocarzilin A通过靶向reticulon 4介导的内质网应激诱导细胞凋亡和线粒体紊乱。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-16 DOI: 10.1038/s41420-025-02560-3

A T Jauch, J Sailer, J Braun, E Czeslik, J Geyer, C Eberhagen, A M Vollmar, H Zischka, S A Sieber, S Zahler

{"title":"Neocarzilin A induces apoptosis and mitochondrial disturbance by targeting reticulon 4-mediated endoplasmic reticulum stress.","authors":"A T Jauch, J Sailer, J Braun, E Czeslik, J Geyer, C Eberhagen, A M Vollmar, H Zischka, S A Sieber, S Zahler","doi":"10.1038/s41420-025-02560-3","DOIUrl":"10.1038/s41420-025-02560-3","url":null,"abstract":"Natural compounds are a valuable source of highly active biomolecules for the discovery of innovative drug targets as well as drug leads. The natural compound neocarzilin A (NCA) exhibits pronounced antiproliferative and antimigratory activity, which we previously ascribed to the target proteins vesicle amine transporter protein 1 (VAT-1) and bone marrow stromal antigen 2 (BST-2). We here additionally demonstrate the perturbation of mitochondrial functions (fragmentation of mitochondrial networks, ultrastructural changes, increased Opa1 splicing, loss of mitochondrial membrane potential, and excessive ROS generation) upon treatment with NCA. We observe impairment of the electron transfer chain and diminished ATP synthesis. Furthermore, NCA triggers apoptosis via activation of caspase-8, enhanced Bid processing, and cytochrome c release from mitochondria into the cytosol, leading to the activation of caspase-3 and -9 and, finally, PARP cleavage and DNA fragmentation. Endoplasmic reticulum (ER) stress is induced by treatment with NCA, and subsequently, the unfolded protein response (UPR) via the protein kinase r-like ER kinase (PERK) branch is prompted. Proteomic ABPP data indicate reticulon 4 (Rtn4, Nogo), an ER-located protein mainly involved in shaping ER tubules and maintaining proper ER function, as a promising hit to explain those effects. This novel molecular target was verified by co-staining of the target probe NC-4 and Rtn4, as well as RNA interference experiments, which resulted in reduced responsiveness of HeLa cells to NCA treatment. We propose NCA as a powerful tool to study the biology of Rtn4, and to develop more specific modulators of reticulons in the future. Furthermore, we introduce-to our knowledge-the first small molecular modulator of reticulon proteins.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"278"},"PeriodicalIF":6.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 role and mechanism of fatty acid oxidation in cancer drug resistance. 脂肪酸氧化在肿瘤耐药中的作用及机制。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2025-06-13 DOI: 10.1038/s41420-025-02554-1

Yun Lei, Shuang Cai, Jia-Kui Zhang, Si-Qi Ding, Zhan-He Zhang, Chun-Dong Zhang, Dong-Qiu Dai, Yong-Shuang Li

引用次数: 0