Cell Death & Disease最新文献_第10页

Roles of the phagocytosis checkpoint in radiotherapy. 吞噬检查点在放射治疗中的作用。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-20 DOI: 10.1038/s41419-025-07921-5

Yulan Kui, Fan Tong, Ruiguang Zhang, Jian Wang, Xiaorong Dong

{"title":"Roles of the phagocytosis checkpoint in radiotherapy.","authors":"Yulan Kui, Fan Tong, Ruiguang Zhang, Jian Wang, Xiaorong Dong","doi":"10.1038/s41419-025-07921-5","DOIUrl":"https://doi.org/10.1038/s41419-025-07921-5","url":null,"abstract":"Radiotherapy is widely used in cancer treatment in both curative and palliative care due to its good safety profile and broad clinical availability. It not only directly destroys tumor cells by damaging their DNA but also plays a critical immunomodulatory role, making it a potential combination partner for immunotherapy. Radiotherapy-induced immune effects are complex. They could enhance antitumor immunity by releasing tumor antigens but also promote tumor immune evasion by adaptively regulating immunosuppressive molecules, such as phagocytosis checkpoints. However, the effects of radiotherapy on phagocytosis checkpoints are not fully elaborated compared to T cell-associated immune checkpoints. Phagocytosis checkpoints are regulated by a series of receptor-ligand binding molecules, respectively on the tumor cells and phagocytes, which mediate pro-phagocytosis or anti-phagocytosis signals, modulate tumor antigen presentation, and further determine the infiltration of tumor-specific cytotoxic T cells in the tumor microenvironment. Radiotherapy regulates the different phagocytosis checkpoints on the tumor cells and phagocytes to modulate phagocytic clearance and reshape the irradiated tumor microenvironment. Therefore, radiotherapy in combination with phagocytosis checkpoints-associated immunotherapy can be a promising antitumor approach by considering the type, dose, and sequence of this combinatory regimen as well as the biomarkers for patient selection. This review attempts to summarize the cross-effects of radiotherapy and phagocytosis checkpoints and their combination strategies to enhance the efficiency of radiotherapy and improve the survival of cancer patients. Opportunities built on the roles of the phagocytosis checkpoint in radiotherapy are duly warranted.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"630"},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944462","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

USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma. USP7通过稳定胶质母细胞瘤中的MGMT促进替莫唑胺耐药性。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-20 DOI: 10.1038/s41419-025-07969-3

Jiabing Li, Xiaorong Feng, Zhaohui Liu, Yunfang Deng, Zhiming Sun, Bei Chen, Lihui Wu, Xiaolong Wang, Lin Miao, Liyuan Zeng, Lei Hu, Yuming He, Ying Sheng, Yue Liu, Yu Zhao

{"title":"USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.","authors":"Jiabing Li, Xiaorong Feng, Zhaohui Liu, Yunfang Deng, Zhiming Sun, Bei Chen, Lihui Wu, Xiaolong Wang, Lin Miao, Liyuan Zeng, Lei Hu, Yuming He, Ying Sheng, Yue Liu, Yu Zhao","doi":"10.1038/s41419-025-07969-3","DOIUrl":"https://doi.org/10.1038/s41419-025-07969-3","url":null,"abstract":"Glioblastoma (GBM), a World Health Organization (WHO) grade IV glioma, is one of the most lethal brain tumors, with a poor prognosis and limited treatment options. Temozolomide (TMZ), a first-line chemotherapeutic agent, often proves ineffective due to resistance and toxicity associated with overexpressed O6-methylguanine-DNA-methyltransferase (MGMT). In this study, we identified ubiquitin-specific protease 7 (USP7) as a nuclear regulator of MGMT stability and TMZ resistance. USP7 binds directly to MGMT via its UBL domain, counteracts K48-linked ubiquitin chains, and prevents MGMT proteasomal degradation. This functional relationship is further supported by their nuclear colocalization. Strikingly, this study, together with previous findings, establishes USP7 as a key integrator of all three major alkylation repair pathways through its role in stabilizing alkylation repair proteins. USP7 stabilizes MGMT through a dual mechanism, thereby modulating the direct reversal repair pathway. Inhibition or knockdown of USP7 reduces MGMT levels, as well as those of XPC, ALKBH2, and ALKBH3, impairs DNA repair capacity, and sensitizes GBM cells to TMZ, enabling effective treatment with reduced TMZ dosages. Clinically, tissue microarray analyses reveal that USP7 and MGMT co-overexpression in GBM correlates with poor patient survival. Collectively, our results uncover a new and direct role for USP7 in MGMT-mediated direct reversal repair and TMZ resistance, positioning USP7 as a distinctive integrator of alkylation repair pathways. Targeting USP7 provides mechanistic insights into regulating diverse alkylation repair pathways and offers a strategy to enhance the efficacy of combination chemotherapies, including TMZ and other alkylating agents, by modulating distinct repair mechanisms in GBM.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"631"},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944429","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

FGF15/FGFR4 signaling suppresses M1 macrophage polarization and multi-organ inflammation in septic mice by inhibiting H3K18 lactylation-driven Irf7 expression through NF2-Hippo activation. FGF15/FGFR4信号通过NF2-Hippo激活抑制H3K18乳酸化驱动的Irf7表达，从而抑制脓毒症小鼠M1巨噬细胞极化和多器官炎症。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-19 DOI: 10.1038/s41419-025-07962-w

Bo Li, Jiayu Li, Zexiang Zhu, Yong Tang, Yun Zhou, Geshu Du, Xing Li

{"title":"FGF15/FGFR4 signaling suppresses M1 macrophage polarization and multi-organ inflammation in septic mice by inhibiting H3K18 lactylation-driven Irf7 expression through NF2-Hippo activation.","authors":"Bo Li, Jiayu Li, Zexiang Zhu, Yong Tang, Yun Zhou, Geshu Du, Xing Li","doi":"10.1038/s41419-025-07962-w","DOIUrl":"10.1038/s41419-025-07962-w","url":null,"abstract":"M1 macrophage polarization plays a key role in the onset and progression of sepsis. Fibroblast growth factor 15 (FGF15) suppresses septic inflammation through its FGF receptor 4 (FGFR4); however, the underlying mechanisms are largely unclear. In this study, we evaluated the anti-inflammatory effects of recombinant FGF15 (rFGF15) in cecal ligation and puncture (CLP)-induced septic mice in vivo, as well as lipopolysaccharide (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 macrophages in vitro. We observed that rFGF15 suppressed M1 macrophage polarization and associated inflammatory responses in both CLP-induced septic mice and LPS-stimulated BMDMs and RAW264.7 macrophages. Additionally, macrophage-depleted CLP mice transplanted with LPS-stimulated BMDMs pre-treated with rFGF15 exhibited reduced multi-organ inflammation and enhanced survival compared to those receiving LPS-stimulated BMDMs without rFGF15 treatment. Mechanistically, FGF15 activated the neurofibromin 2 (NF2)-Hippo pathway through FGFR4, leading to the inhibition of glycolysis, lactate production, and histone H3K18 lactylation. This led to reduced expression of interferon regulatory factor 7 (Irf7), a key regulator of type I interferon responses. In conclusion, FGF15 suppresses M1 macrophage polarization and associated inflammatory responses in sepsis by activating the NF2-Hippo pathway, thereby inhibiting H3K18 lactylation-driven Irf7 expression. FGF15 holds promise as a potential innovative therapy for sepsis.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"628"},"PeriodicalIF":9.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871683","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

Biogenesis, functional roles, and pathological implications of migrasomes. 偏头痛的生物发生、功能作用和病理意义。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-19 DOI: 10.1038/s41419-025-07943-z

Xuexue Liu, Dun Liu, Heng Zhao, Kangxue Wu, Shaoping Yin, Xian Yang, Chuanqin Chen, Xiaolong Ma, Yonghuan Mao, Haixia Zhang, Lihua Shao, Siliang Wang, Xiao Du

引用次数: 0

Targeting PRDX1 impairs acute myeloid leukemic blasts and stem cells by disrupting redox homeostasis. 靶向PRDX1通过破坏氧化还原稳态损害急性髓系白血病母细胞和干细胞。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-18 DOI: 10.1038/s41419-025-07831-6

Zhenghao Li, Guangci Liu, Ziren Chen, Keming Li, Zhe Yu, Chao He, Xinyu Ying, Danling Huang, Chengtian Tao, Sajid Khan, Yimeng Wang, Fang-Lin Zhang, Huan Li, Yun Chen, Jingfeng Zhou, Li Yu, Thomas J Kipps, Yongxian Cheng, Suping Zhang

{"title":"Targeting PRDX1 impairs acute myeloid leukemic blasts and stem cells by disrupting redox homeostasis.","authors":"Zhenghao Li, Guangci Liu, Ziren Chen, Keming Li, Zhe Yu, Chao He, Xinyu Ying, Danling Huang, Chengtian Tao, Sajid Khan, Yimeng Wang, Fang-Lin Zhang, Huan Li, Yun Chen, Jingfeng Zhou, Li Yu, Thomas J Kipps, Yongxian Cheng, Suping Zhang","doi":"10.1038/s41419-025-07831-6","DOIUrl":"10.1038/s41419-025-07831-6","url":null,"abstract":"Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis and limited therapeutic options. Leukemic stem cells (LSCs), which drive disease progression and confer resistance to therapy, pose a significant challenge to conventional treatment strategies. In this study, we identified and characterized the inhibitory mechanisms of TH37, a small molecule derived from traditional Chinese medicine, which selectively targets AML blasts and LSCs. Our analyses identified peroxiredoxin 1 (PRDX1), an enzyme that catalyzes the breakdown of hydrogen peroxide (a reactive oxygen species), as the primary molecular target of TH37. We demonstrated that TH37 directly interacts with PRDX1, inhibiting its enzymatic activity and thereby elevating intracellular reactive oxygen species levels in AML cells. PRDX1 was found to be overexpressed in AML, and its expression correlated with poor prognosis and the activation of AML- and cancer-associated pathways. Targeting PRDX1, either through lentiviral short-hairpin RNA-mediated silencing or TH37 treatment, induced apoptosis, reduced colony formation, and impaired the engraftment and growth of AML cells in immunodeficient mouse models. Furthermore, TH37 synergized with conventional chemotherapeutic agent to significantly reduce the viability and colony-forming capacity of AML cells. These findings demonstrate the critical role of PRDX1 in AML pathogenesis and highlight its potential as a key therapeutic target to improve clinical outcomes for AML patients.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"627"},"PeriodicalIF":9.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871685","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

Unraveling the Role of METTL3 in Helicobacter pylori-induced gastritis via m6A-CXCL1/NF-κB modulation. METTL3通过m6A-CXCL1/NF-κB调控在幽门螺杆菌诱导的胃炎中的作用

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-18 DOI: 10.1038/s41419-025-07841-4

Qiutong Lu, Zhaopeng Wang, Shuixian Cao, Huan Wang, Nianshuang Li, Yi Hu, Wuhui Ding, Wei Zuo, Junbo Hong

引用次数: 0

Inhibition of ATM enhances the immunogenicity of triple-negative breast cancer by promoting MHC-I expression. 抑制ATM通过促进MHC-I的表达来增强三阴性乳腺癌的免疫原性。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-18 DOI: 10.1038/s41419-025-07944-y

Jiazhen Li, Chenying Liu, Xiaolong Qian, Xiaozi Wang, Hui Sun, Lu Wang, Huiqin Xue, Yuanming Song, Jiamei Liu, Yafang Zhao, Yumian Jia, Fengxia Qin, Tianhua Zhang, Xiaojing Guo

{"title":"Inhibition of ATM enhances the immunogenicity of triple-negative breast cancer by promoting MHC-I expression.","authors":"Jiazhen Li, Chenying Liu, Xiaolong Qian, Xiaozi Wang, Hui Sun, Lu Wang, Huiqin Xue, Yuanming Song, Jiamei Liu, Yafang Zhao, Yumian Jia, Fengxia Qin, Tianhua Zhang, Xiaojing Guo","doi":"10.1038/s41419-025-07944-y","DOIUrl":"10.1038/s41419-025-07944-y","url":null,"abstract":"The immunotherapy has achieved some efficacy in triple-negative breast cancer (TNBC), but the benefit population is limited, primarily due to an abnormal immune microenvironment. Thus, it is necessary to explore new molecular targets to enhance the immunogenicity of TNBC cells and improve their responsiveness to immunotherapy. We found that a key component of the DNA repair system, Ataxia telangiectasia mutated (ATM), may function as an immune response inhibitor. In this study, the inverse correlation between ATM and CD8+ T cells and tumor-infiltrating lymphocytes (TILs) was confirmed by immunochemical staining of 191 TNBC specimens. Subsequently, inhibition of ATM increased the expression of major histocompatibility complex I (MHC-I) and enhanced the infiltration and cytotoxic activity of CD8+ T cells by Western blot and flow cytometry analysis. In addition, we further confirmed that the MHC-I upregulation induced by ATM inhibition depends on the activation of the c-Jun/TNF-α/p-STAT1 pathway. Animal studies have shown that ATM deficiency delays tumor growth and sensitizes tumors to PD-1 blockade and radiotherapy. This study reveals a new mechanism by which ATM negatively regulates MHC-I by inhibiting the c-Jun/TNF-α/p-STAT1 pathway in TNBC, and shows an important role in mediating CD8+ T cells infiltration and regulating the \"heat\" of the immune microenvironment. The combination of ATM inhibitors with radiotherapy and Immune-checkpoint blockade (ICB) therapies may be a new strategy for TNBC treatment.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"624"},"PeriodicalIF":9.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871684","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

AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria. AMPK调节ARF1定位到膜接触位点，促进脂肪酸在脂滴和线粒体之间的转移。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-18 DOI: 10.1038/s41419-025-07957-7

Lupeng Chen, Yue Liu, Junzhi Zhang, Tongxing Song, Jian Wu, Zhuqing Ren

{"title":"AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria.","authors":"Lupeng Chen, Yue Liu, Junzhi Zhang, Tongxing Song, Jian Wu, Zhuqing Ren","doi":"10.1038/s41419-025-07957-7","DOIUrl":"10.1038/s41419-025-07957-7","url":null,"abstract":"Lipid droplet (LD) -mitochondrion contacts play a crucial role in regulating energy metabolism and fatty acid oxidation in skeletal muscle cells. However, the proteins that regulate these interactions remain poorly understood. Here, we demonstrate that the binding between ADP-ribosylation factor 1(ARF1) and perilipin2 (Plin2) regulates LD-mitochondrion contacts under starvation conditions, facilitating the transfer of fatty acids from LDs to mitochondria. In C2C12 cells, starvation increased ARF1's GTP-binding activity and its localization to mitochondria, enhancing ARF1's binding to Plin2 and facilitating fatty acid flow from LDs to mitochondria. In contrast, knockdown of ARF1 reduced LD-mitochondrion interactions and blocked fatty acids transfer. Additionally, ARF1-mediated interactions were regulated by AMPK; inhibiting AMPK activity reduced ARF1 localization to LDs and mitochondria, and blocked LD-mitochondrion interactions. In mice, starvation increased ARF1 expression in muscle tissue and LD-mitochondrion contacts. Conversely, inhibiting ARF1 led to lipid accumulation in muscle tissue. In conclusion, our work suggests that ARF1 is a critical regulator of LD-mitochondrion interactions and plays a significant role in energy metabolism regulation in skeletal muscle.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"623"},"PeriodicalIF":9.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871681","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

Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication. 肠细胞中的辅助素通过细胞间通讯控制肠道内稳态。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-18 DOI: 10.1038/s41419-025-07954-w

Runqi Wang, Zhengran Li, Jing Wei, Ruiyan Kong, Xuejing Ren, Hang Zhao, Danjie Zhang, Xiyue Tao Liu, Zhouhua Li

{"title":"Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication.","authors":"Runqi Wang, Zhengran Li, Jing Wei, Ruiyan Kong, Xuejing Ren, Hang Zhao, Danjie Zhang, Xiyue Tao Liu, Zhouhua Li","doi":"10.1038/s41419-025-07954-w","DOIUrl":"10.1038/s41419-025-07954-w","url":null,"abstract":"Residential stem cells sense extrinsic and intrinsic signals to proliferate accordingly to maintain homeostasis. However, how differentiated cells control stem cell proliferation still remains elusive. Here, we find that Auxilin (Aux) maintains enterocyte (EC) integrity to prevent unlimited intestinal stem cell (ISC) proliferation. Depleting aux in ECs leads to excessive ISC proliferation and intestinal homeostasis disruption. Ectopic cytokine production from dying aux-depleted ECs activates JAK/STAT signaling and promotes ISC proliferation. Mechanistically, Aux facilitates anterograde ER-to-Golgi apparatus (GA) vesicle transport by associating with COPII coatomer. Further, the presentation of cell adhesion molecules (CAMs) by ER-to-GA transport is required for intestinal homeostasis. Together, these data demonstrate that Aux maintains EC integrity by mediating ER-to-GA trafficking of CAMs to restrain excessive ISC proliferation. Thus our study uncovers the underlying mechanism of how differentiated cells control stem cell proliferation through inter-cell communication during tissue homeostasis and pathogenesis.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"626"},"PeriodicalIF":9.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871682","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

TRIM31 triggers colorectal carcinogenesis and progression by maintaining YBX1 protein stability through ubiquitination modification. TRIM31通过泛素化修饰维持YBX1蛋白的稳定性，从而触发结直肠癌的发生和进展。

IF 9.6 1区生物学

Cell Death & Disease Pub Date : 2025-08-16 DOI: 10.1038/s41419-025-07922-4

Xiaoqing Li, Ying Wu, Jiahao Guo, Peng Huang, Qiuhui Li, Zhongyu Gao, Yanming Hu, Aidi Gao, Ming Sun, Han Min, Jundong Zhou

{"title":"TRIM31 triggers colorectal carcinogenesis and progression by maintaining YBX1 protein stability through ubiquitination modification.","authors":"Xiaoqing Li, Ying Wu, Jiahao Guo, Peng Huang, Qiuhui Li, Zhongyu Gao, Yanming Hu, Aidi Gao, Ming Sun, Han Min, Jundong Zhou","doi":"10.1038/s41419-025-07922-4","DOIUrl":"10.1038/s41419-025-07922-4","url":null,"abstract":"Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, and one of the leading causes of cancer-related deaths worldwide. However, the molecular mechanisms underlying CRC development and progression have not been fully elucidated until now. Emerging studies have shown that post-translational modifications of proteins, especially ubiquitination modifications, play an important role in tumorigenesis and progression. Here we identified that the E3 ligase TRIM31, a member of the TRIM (Tripartite Motif) family proteins, is highly expressed during colorectal inflammation-cancer transformation and is associated with poor prognosis in CRC patients. Knockdown of TRIM31 expression led to the suppression of CRC cell proliferation and migration in vitro, tumor formation and metastatic ability in vivo. TRIM31 interacts with YBX1 and catalyses the Lys63 (K63) linkage polyubiquitination of Lys81 on YBX1, which ultimately leads to the stabilization of the YBX1 protein. YBX1 further enhances the stabilization of mRNAs for EREG, GAS6, and MAFG through both m5C site-dependent and -independent recognition routes. In addition, activation of NF-κB promotes the binding of P65 to the promoter region of TRIM31 to activate the transcription of the TRIM31 gene. Furthermore, TRIM31 facilitates the entry of P65 into the nucleus, which in turn creates a positive feedback pathway that promotes inflammatory-carcinogenic transformation and tumorigenesis of colorectal. Our findings indicate that TRIM31 may be an important factor driving colorectal carcinogenesis, providing a potential target for intervention in CRC targeted therapy.","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"621"},"PeriodicalIF":9.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862117","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