Cell Death & Disease最新文献

Correction: Ubiquitin-specific protease 25 ameliorates ulcerative colitis by regulating the degradation of phosphor-STAT3.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-26 DOI: 10.1038/s41419-025-07491-6

Zhengru Liu, Jian Liu, Yuping Wei, Jinting Li, Jixiang Zhang, Rong Yu, Qian Yang, Yinglei Miao, Weiguo Dong

引用次数: 0

Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-26 DOI: 10.1038/s41419-025-07562-8

Danping Sun, Xiaohan Cui, Wenshuo Yang, Meng Wei, Zhibo Yan, Mingxiang Zhang, Wenbin Yu

{"title":"Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.","authors":"Danping Sun, Xiaohan Cui, Wenshuo Yang, Meng Wei, Zhibo Yan, Mingxiang Zhang, Wenbin Yu","doi":"10.1038/s41419-025-07562-8","DOIUrl":"https://doi.org/10.1038/s41419-025-07562-8","url":null,"abstract":"The treatment of gastric cancer remains challenging, with immunotherapy serving as a critical component of the holistic approach to its treatment. The results of this study indicated that statins could decrease the serum levels of interleukin-enhancing binding factor 3 (ILF3) and programmed cell death ligand 1(PD-L1) in GC patients and improve their prognosis. Functional experiments demonstrated that simvastatin induced ferroptosis by inhibiting ILF3 in GC cells and enhanced the killing effect of activated CD8+ T cells on GC cells. The CUT&Tag assay revealed that, mechanistically, simvastatin inhibited ILF3 expression by reducing the acetylation level at residue site H3K14 in ILF3. Next-generation sequencing and Kyoto Encyclopedia of Genes and Genomes analysis revealed that ILF3 regulated PD-L1 expression through the DEPTOR/mTOR signaling pathway. Overall, simvastatin induced ferroptosis in GC cells by inhibiting ILF3 expression while promoting the activation of CD8+ T cells to augment antitumor immune responses, thereby facilitating synergistic immunotherapy.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"208"},"PeriodicalIF":8.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718090","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}

引用次数: 0

TRMT10A regulates tRNA-ArgCCT m¹G9 modification to generate tRNA-derived fragments influencing vasculogenic mimicry formation in glioblastoma.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-26 DOI: 10.1038/s41419-025-07548-6

Deng Wei, Bei Zhai, Hui Zeng, Long Liu, Han Gao, Shiqi Xiang, Xiaobai Liu, Jun Ma, Yang Lin, Yilong Yao, Ping Wang

{"title":"TRMT10A regulates tRNA-ArgCCT m1G9 modification to generate tRNA-derived fragments influencing vasculogenic mimicry formation in glioblastoma.","authors":"Deng Wei, Bei Zhai, Hui Zeng, Long Liu, Han Gao, Shiqi Xiang, Xiaobai Liu, Jun Ma, Yang Lin, Yilong Yao, Ping Wang","doi":"10.1038/s41419-025-07548-6","DOIUrl":"https://doi.org/10.1038/s41419-025-07548-6","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system tumor. The formation of vasculogenic mimicry (VM) in GBM is closely related to poor patient prognosis. Therefore, it is urgently necessary to explore the mechanisms that promote VM formation in GBM and identify therapeutic targets. CGGA data analysis revealed that TRMT10A expression is significantly downregulated in WHO grade IV primary glioma samples compared to grade II samples, consistent with the protein expression levels. Additionally, GBM patients with low TRMT10A expression have poorer prognoses. In human glioma cells, TRMT10A expression is significantly lower than in human astrocytes. Knockdown of TRMT10A reduces m1G9 modification of tRNA-ArgCCT, upregulates tRF-22 expression, and promotes glioma cell proliferation, migration, invasion, and tube formation. Overexpression of tRF-22 in glioma cells significantly downregulates MXD1 expression. tRF-22 negatively regulates MXD1 expression by binding to its 3'UTR, reducing MXD1's transcriptional inhibition of HIF1A, thereby promoting glioma cell proliferation, migration, invasion, and tube formation. Overexpression of TRMT10A combined with tRF-22 inhibition significantly reduces the number of VM channels and inhibits tumor growth in xenograft models in nude mice. This study elucidates the mechanism by which TRMT10A affects VM formation in glioma and provides a novel therapeutic target for GBM.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"209"},"PeriodicalIF":8.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718093","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}

引用次数: 0

XIAP promotes metastasis of bladder cancer cells by ubiquitylating YTHDC1.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07545-9

Ning Sun, Sijia Wang, Jianting Liu, Peipei Zhang, Yixin Chang, Hongyan Li, Kun Zhao, Yijie Liu, Mingzhi Huang, Yan Hu, Zhenni Lin, Yongyong Lu, Guosong Jiang, Wei Chen, Chuanshu Huang, Honglei Jin

{"title":"XIAP promotes metastasis of bladder cancer cells by ubiquitylating YTHDC1.","authors":"Ning Sun, Sijia Wang, Jianting Liu, Peipei Zhang, Yixin Chang, Hongyan Li, Kun Zhao, Yijie Liu, Mingzhi Huang, Yan Hu, Zhenni Lin, Yongyong Lu, Guosong Jiang, Wei Chen, Chuanshu Huang, Honglei Jin","doi":"10.1038/s41419-025-07545-9","DOIUrl":"https://doi.org/10.1038/s41419-025-07545-9","url":null,"abstract":"X-linked inhibitor of apoptosis protein (XIAP), a member of the IAP family, is overexpressed in a variety of tumors and plays an important role in tumor progression. Increasing evidence suggests that XIAP promotes metastasis of bladder cancer but the underlying mechanism is not very clear. The RNA N6-methyladenosine (m6A) reader YTHDC1 regulates RNA splicing, nuclear transport, and mRNA stability and is a potential tumor target; however, its ubiquitin E3 ligase has not been described. In this study, screening of proteins that specifically interact with XIAP identified YTHDC1 as its degradation substrate. Ectopic overexpression of XIAP promoted degradation of YTHDC1, and knockout of XIAP upregulated YTHDC1, which inhibited metastasis of bladder cancer. Furthermore, YTHDC1 reduced the expression of matrix metalloproteinase-2 (MMP-2) by destabilizing its mRNA. These experiments revealed that XIAP promotes ubiquitination of YTHDC1, positively regulating expression of the MMP-2 and promoting metastasis of bladder cancer. Collectively, these findings demonstrate that XIAP is a critical regulator of YTHDC1 and pinpoint the XIAP/YTHDC1/MMP-2 axis as a promising target for the treatment of bladder cancer.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"205"},"PeriodicalIF":8.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708202","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}

引用次数: 0

Hypomethylation induced overexpression of PLOD3 facilitates colorectal cancer progression through TM9SF4-mediated autophagy.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07503-5

Renzhong Zhu, Chuanxin Tian, Nan Gao, Zhiqiang Li, Sheng Yang, Yue Zhang, Ming Zhou, Yueming Sun, Chuan Zhang, Kangpeng Jin

{"title":"Hypomethylation induced overexpression of PLOD3 facilitates colorectal cancer progression through TM9SF4-mediated autophagy.","authors":"Renzhong Zhu, Chuanxin Tian, Nan Gao, Zhiqiang Li, Sheng Yang, Yue Zhang, Ming Zhou, Yueming Sun, Chuan Zhang, Kangpeng Jin","doi":"10.1038/s41419-025-07503-5","DOIUrl":"https://doi.org/10.1038/s41419-025-07503-5","url":null,"abstract":"Colorectal cancer (CRC) ranks among the primary causes of human mortality globally. Numerous studies have highlighted the significant role of PLOD3 in the progression of various cancers. However, the exact function and underlying mechanisms of PLOD3 in CRC remains incompletely understood. To investigate the expression of PLOD3, qRT‒PCR, immunohistochemistry and western blotting were utilized to analyze the expression of PLOD3 in CRC tissues and adjacent normal tissues. Functional assays were conducted to assess the roles of PLOD3 both in vitro and in vivo. To elucidate the potential mechanism of PLOD3 in CRC, a range of techniques, including coimmunoprecipitation, immunofluorescence, CHX pulse-chase, and ubiquitination assays were used. As the results indicated, hypomethylation of the PLOD3 promoter leads to its over- expression in CRC, and elevated PLOD3 levels are associated with a poor prognosis. Both in vitro and in vivo models demonstrated that PLOD3 enhances CRC cell proliferation, invasion, and migration. Furthermore, through mechanistic studies, TM9SF4 was identified as a protein that interacts with PLOD3 and contributes to CRC progression by promoting autophagy. Additionally, PLOD3 could be secreted by CRC cells and secreted PLOD3 could promote CRC cells migration and invasion. These results demonstrated that PLOD3 promotes CRC progression through the PLOD3/TM9SF4 axis and could be a potential biomarker and treatment target for CRC.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"206"},"PeriodicalIF":8.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708851","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}

引用次数: 0

ATP6AP1 promotes cell proliferation and tamoxifen resistance in luminal breast cancer by inducing autophagy.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07534-y

Zhengwei Yan, Aidi Huang, Dongwen Ma, Chenao Hong, Shengmiao Zhang, Luling He, Hai Rao, Shiwen Luo

{"title":"ATP6AP1 promotes cell proliferation and tamoxifen resistance in luminal breast cancer by inducing autophagy.","authors":"Zhengwei Yan, Aidi Huang, Dongwen Ma, Chenao Hong, Shengmiao Zhang, Luling He, Hai Rao, Shiwen Luo","doi":"10.1038/s41419-025-07534-y","DOIUrl":"https://doi.org/10.1038/s41419-025-07534-y","url":null,"abstract":"Autophagy is a highly conserved cellular process essential for maintaining cellular homeostasis and influencing cancer development. Lysosomal acidification and autophagosome-lysosome fusion are two important steps of autophagy degradation that are tightly regulated. Although many key proteins that regulate these two events have been identified, the effector proteins that co-regulate both steps remain to be explored. ATP6AP1, an accessory subunit of V-ATPase, plays a critical role in the assembly and regulation of V-ATPase. However, the function of ATP6AP1 in autophagy remains unknown, and the role of ATP6AP1 in cancer is still poorly understood. In this study, we found that ATP6AP1 is overexpressed in luminal breast cancer tissues and promotes the proliferation and tamoxifen resistance of luminal breast cancer cells both in vitro and in vivo. We also observed that high ATP6AP1 expression correlates with poor overall patient survival. Our research further revealed that ATP6AP1 enhances tamoxifen resistance by activating autophagy. Mechanistically, ATP6AP1 promotes autophagy by regulating both lysosomal acidification and autophagosome-lysosome fusion. Remarkably, ATP6AP1 induces lysosomal acidification through the regulation of V-ATPase assembly and facilitates autophagosome-lysosome fusion by enhancing the interaction between Rab7 and the HOPS complex. Together, our studies identify ATP6AP1 as a crucial regulator of autophagy, potentially serving as a valuable prognostic marker or therapeutic target in human luminal breast cancer.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"201"},"PeriodicalIF":8.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708790","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}

引用次数: 0

GLI2 inhibits cisplatin sensitivity in gastric cancer through DEC1/ZEB1 mediated EMT.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07564-6

Wenshuai Zhu, Jingguo Sun, Fubo Jing, Yuanxin Xing, Muhua Luan, Zhaotian Feng, Xiaoli Ma, Yunshan Wang, Yanfei Jia

{"title":"GLI2 inhibits cisplatin sensitivity in gastric cancer through DEC1/ZEB1 mediated EMT.","authors":"Wenshuai Zhu, Jingguo Sun, Fubo Jing, Yuanxin Xing, Muhua Luan, Zhaotian Feng, Xiaoli Ma, Yunshan Wang, Yanfei Jia","doi":"10.1038/s41419-025-07564-6","DOIUrl":"https://doi.org/10.1038/s41419-025-07564-6","url":null,"abstract":"Cisplatin (CDDP) based chemotherapy has emerged as the predominant therapeutic regimen for patients with advanced gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which results in poor prognosis of patients. GLI2, a key transcription factor in the Hedgehog (Hh) signaling pathway, is regarded as a target for cancer therapy. However, the significance of GLI2 for CDDP resistance in GC has not been well established. Here, we show that GLI2 expression was upregulated in EMT-type GC and associated with poor prognosis. GLI2 promotes proliferation, migration, and CDDP resistance of GC cells by inducing EMT. In terms of mechanism, GLI2 binds to the promoter region of DEC1 and enhances its expression, thereby co-transcriptionally regulating ZEB1 expression. Animal experiments have demonstrated that both GLI2 knockdown and GLI2 inhibitor significantly enhance CDDP sensitivity in GC. Our data not only identify a novel GLI2/DEC1/ZEB1/EMT pathway in GC CDDP resistance but also provide novel strategies to treat GC in the future.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"204"},"PeriodicalIF":8.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708740","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}

引用次数: 0

CARM1 S217 phosphorylation by CDK1 in late G2 phase facilitates mitotic entry.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07533-z

Yena Cho, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

引用次数: 0

Overexpression of βTrCP1 elicits cell death in cisplatin-induced senescent cells.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-25 DOI: 10.1038/s41419-025-07556-6

Alejandro Belmonte-Fernández, Joaquín Herrero-Ruíz, M Cristina Limón-Mortés, Carmen Sáez, Miguel Á Japón, Mar Mora-Santos, Francisco Romero

{"title":"Overexpression of βTrCP1 elicits cell death in cisplatin-induced senescent cells.","authors":"Alejandro Belmonte-Fernández, Joaquín Herrero-Ruíz, M Cristina Limón-Mortés, Carmen Sáez, Miguel Á Japón, Mar Mora-Santos, Francisco Romero","doi":"10.1038/s41419-025-07556-6","DOIUrl":"https://doi.org/10.1038/s41419-025-07556-6","url":null,"abstract":"Senescence is a non-proliferative cellular state derived from aging or in response to exogenous insults, such as those that cause DNA damage. As a result of cancer treatments like cisplatin, certain tumor cells may undergo senescence. However, rather than being beneficial for patients, this is detrimental because these cells might proliferate again under specific conditions and, more importantly, because they synthesize and secrete molecules that promote the proliferation of nearby cells. Therefore, to achieve complete tumor remission, it is necessary to develop senolytic compounds to eliminate senescent cells. Here, we studied the role of βTrCP1 in cell proliferation and senescence and found that lentiviral overexpression of βTrCP1 induces the death of senescent cells obtained after cisplatin treatment in both two-dimensional cell cultures and tumorspheres. Mechanistically, we demonstrated that overexpression of βTrCP1 triggers proteasome-dependent degradation of p21 CIP1, allowing damaged cells to progress through the cell cycle and consequently die. Furthermore, we identified nucleophosmin 1 (NPM1) as the intermediary molecule involved in the effect of βTrCP1 on p21 CIP1. We determined that increased amounts of βTrCP1 partially retains NPM1 in the nucleoli, preventing it from associating with p21 CIP1, thus leaving it unprotected from degradation by the proteasome. These results have allowed us to discover a potential new target for senolytic drugs, as retaining NPM1 in the nucleoli under senescent conditions induces cell death.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"203"},"PeriodicalIF":8.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708855","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}

引用次数: 0

Retraction Note to: BRD4 promotes tumor progression and NF-κB/CCL2-dependent tumor-associated macrophage recruitment in GIST.

IF 8.1 1区生物学

Cell Death & Disease Pub Date : 2025-03-24 DOI: 10.1038/s41419-025-07520-4

Zhiming Ma, Jianfeng Mu, Pengfei Sun, Pengda Sun

引用次数: 0