Cell Death Discovery最新文献

{"title":"MLN4924 suppresses tumor metabolism and growth of clear cell renal cell carcinoma by stabilizing nuclear FBP1.","authors":"Yajing Yang, Yan Ma, Shiyin Fan, Jie Zhu, Bin Ye, Ruonan Zhang, Jiaxi Li, Hongchen Li, Zhencang Zheng, Yufeng Li, Lei Lv","doi":"10.1038/s41420-025-02426-8","DOIUrl":"10.1038/s41420-025-02426-8","url":null,"abstract":"<p><p>Fructose-1, 6-bisphosphatase (FBP1) is a tumor suppressor and frequently deficient in various cancers, including clear cell renal cell carcinoma (ccRCC). VHL inactivation mutations are usually observed in ccRCC, which can lead to abnormal activation of the HIF signaling pathway. FBP1 could enter the nucleus and restrain HIF function in a non-enzymatic manner. However, its regulatory mechanism in ccRCC tumorigenesis remains poorly understood. Here, we report that nuclear FBP1 is degraded through the ubiquitin-proteasome pathway, and CUL4B acts as Cullin-RING E3 ubiquitin ligase (CRL) to promote the degradation of FBP1 in nucleus, while the neddylation inhibitor MLN4924 could inactivate CUL4B E3 ligase, block proteasomal degradation of FBP1 and suppress HIF target gene expression, including GLUT1, LDHA, PDK1 and VEGF, leading to decreased glucose uptake and lactate and NADPH production, thereby repressing tumor growth of ccRCC. Furthermore, MLN4924 sensitizes ccRCC to γ-glutamylcysteine synthetase inhibitor Buthionine sulfoximine (BSO) treatment in vivo. Collectively, these findings proposed that MLN4924 could inhibit the tumor growth of VHL deficiency-driven ccRCC by stabilizing FBP1, providing new target and strategy for clinic treatment of ccRCC.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"253"},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149364","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}

{"title":"Shaking culture attenuates circadian rhythms in induced pluripotent stem cells during osteogenic differentiation through the TEAD-Fbxl3-CRY axis.","authors":"Yunyu Fu, Hiroko Okawa, Naruephorn Vinaikosol, Satomi Mori, Phoonsuk Limraksasin, Praphawi Nattasit, Yu Tahara, Hiroshi Egusa","doi":"10.1038/s41420-025-02533-6","DOIUrl":"10.1038/s41420-025-02533-6","url":null,"abstract":"<p><p>Circadian rhythms, which synchronize cellular and organismal activities with the Earth's 24-hour light-dark cycle, are controlled by clock genes. These genes not only regulate metabolic and physiological processes but also influence osteogenesis. Despite extensive research on the genetic control of circadian rhythms, little is known about the mechanisms by which mechanical factors in the extracellular environment affect these rhythms during the osteogenic differentiation of induced pluripotent stem cells (iPSCs). Shaking culture, which promotes the formation of three-dimensional organoid-like constructs from iPSC embryoid bodies (iPSC-EBs), introduces distinct biomechanical forces compared with static adherent culture. This raises the question of how these forces affect the circadian gene expression during osteogenic differentiation. In this study, we investigated the effects of shaking cultures on the circadian rhythm of key clock genes (Clock, Bmal1, and Npas2) in iPSC-EBs. In the adherent culture, iPSC-EBs displayed rhythmic oscillations of the clock genes, which were attenuated in the shaking culture. RNA-seq analysis revealed that the yes-associated protein (YAP)-transcriptional enhanced associate domain (TEAD) transcriptional cascade was activated in the shaking culture. Further investigations using assay for transposase-accessible chromatin with sequencing and chromatin immunoprecipitation assays identified Fbxl3 as a direct target of this transcriptional cascade. Fbxl3 upregulation in the shaking culture enhanced the degradation of CRY proteins, which are essential components of the circadian feedback loop, thereby suppressing clock gene oscillations. In addition, treatment with verteporfin, a YAP-TEAD inhibitor, restored circadian gene oscillations and increased the expression of osteogenic markers in shaking culture. These findings highlight a novel mechanistic link between biomechanical cues and circadian regulation and offer potential insights for optimizing tissue engineering strategies in regenerative medicine.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"252"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141537","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}

{"title":"Correction: The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome.","authors":"Ramla Omar, Michelle Aw Lee, Laura Gonzalez-Trueba, Cameron R Thomson, Uwe Hansen, Spyridonas Lianos, Snoopy Hazarika, Omar Hmeh El Abdallah, Malak A Ammar, Jennifer Cassels, Alison M Michie, Neil J Bulleid, Fransiska Malfait, Tom Van Agtmael","doi":"10.1038/s41420-025-02529-2","DOIUrl":"10.1038/s41420-025-02529-2","url":null,"abstract":"","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"250"},"PeriodicalIF":6.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132248","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}

{"title":"Absence of Rnf126 causes male infertility with multiple morphological abnormalities of the sperm flagella.","authors":"Shengnan Wang, Zihan Qin, Juan Liu, Jie Liu, Qiaohua Xiong, Zexiao Wei, Li Wang, Yuming Cao","doi":"10.1038/s41420-025-02432-w","DOIUrl":"10.1038/s41420-025-02432-w","url":null,"abstract":"<p><p>Male infertility is primarily caused by impaired flagella development, reduced sperm count, and decreased motility. Despite the involvement of many genes in spermatogenesis, the precise processes remain unclear. The critical E3 ubiquitin ligase Rnf126 regulates essential cellular processes through ubiquitination-induced protein degradation. It plays a significant role in DNA repair, immune response, and signaling cascades, underscoring its central importance in maintaining cellular homeostasis. However, the mechanisms by which Rnf126 controls spermatogenesis are not fully understood. This research identifies Rnf126 as a crucial component in sperm flagellar biogenesis and germ cell development. Through genetic lineage tracing, we show that RNF126 is highly expressed in sperm cells and weakly expressed in Sertoli cells. The germ epithelium of RNF126 deficiencies is characterized by a loss of germ cells due to an increase in germ cell apoptosis at various stages of development, which ultimately results in vesiculation of the spermatogenic tubule. Targeting Rnf126 results in different types of germ cells reduction, infertility, and microtubule-associated motor activity failure (MMAF), characterized by spermatozoa with truncated, twisted, and malformed flagella. Detailed ultrastructural studies reveal the extent of flagellar damage in the absence of Rnf126, highlighting its critical role in maintaining flagellar stability. An important finding is the interaction between RNF126 and BAG6, which regulates sperm synthesis and germ cell development. Clinically, reduced RNF126 levels in sperm from individuals with oligoasthenoteratospermia are significantly different from those in fertile individuals. Investigating Rnf126 function in spermatogenesis, together with empirical findings on MMAF presentation, may improve our understanding of the developmental processes involved in sperm flagellum formation and contribute to elucidating the causes of male infertility.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"251"},"PeriodicalIF":6.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132231","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}

{"title":"Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.","authors":"Xiaoxian Zhang, Li Huang, Cheng Li, Jinjuan Yang, Fuyu Duan, Qiang Su, Yuelin Zhang, Meng Kou, Xiaoya Zhou, Liyan Guo, Shaoxiang Chen, Yongxia Niu, Ziyue Li, Sihua Ou, Min Zhang, Kenneth King-Yip Cheng, Jianlong Wu, Xiang Xu, Qizhou Lian","doi":"10.1038/s41420-025-02524-7","DOIUrl":"10.1038/s41420-025-02524-7","url":null,"abstract":"<p><p>Mutations in genes affecting mitochondrial complex I (CI) can lead to mitochondrial cardiomyopathy (MCM) yet no effective treatment. This study sought to determine whether adeno-associated virus 9 (AAV9)-based gene therapy could prevent or rescue Ndufs6 deficiency-induced MCM at different disease stages. Using Ndufs6^gt/gt mice to mimic MCM, cardiac dysfunction was evident at week 4 post-birth, showing reduced ejection fraction, CI activity, increased fibrosis, mitochondrial fission, and disrupted cristae. Neonatal and adult mice were intravenously given AAV9-hNdufs6 (1e14 vg kg^-1). AAV9-hNdufs6 therapy effectively prevented neonatal mice's cardiac dysfunction onset, preserving CI activity and cristae structure for 11 months. In contrast, therapy in adult mice post-disease onset failed to reverse or halt progression of heart dilation and failure after 3 months, showing mitochondrial abnormalities and cardiomyocyte apoptosis. Mechanistically, adult mouse Kupffer cells demonstrated enhanced phagocytic capabilities compared to neonatal mice, with higher expression levels of AAV9 cell surface receptors observed in neonatal mouse hearts, rendering neonatal mice more responsive to AAV9-mediated gene therapy for heart tissue. Additionally, AAV9-hNdufs6 gene therapy initiated at an early stage increased Ndufs6 expression in cardiac tissue, preserved mitochondrial structure and function, prevented cardiomyocyte fibrosis through modulation of the AMPK/Drp1 signaling pathway. In conclusion, early intervention with AAV9-hNdufs6 gene therapy can effectively prevent the onset of MCM, but intervention after disease onset has limited efficacy.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"249"},"PeriodicalIF":6.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118934","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}

{"title":"Acyl post-translational modification of proteins by metabolites in cancer cells.","authors":"Xudong Wang, Yining Guo, Yutian Fu, Chen Zhang, Weiwu Chen, Xinyu Tang, Yanlan Yu, Yicheng Chen, Guoqing Ding, Jie Zhang","doi":"10.1038/s41420-025-02535-4","DOIUrl":"10.1038/s41420-025-02535-4","url":null,"abstract":"<p><p>The relationship between metabolism and cancer is a major focus of current research, with an increasing number of studies highlighting the significant role of various metabolites in tumor cells, such as lactate, acetic acid, lysine, serine, tryptophan, palmitic acid, succinate, etc. These metabolites are involved in numerous biological processes within tumor cells, including transcription, translation, post-translational modification (PTM) of proteins, cell cycle regulation, and metabolism, thereby modulating tumor proliferation, migration, and drug resistance. Metabolite-mediated PTMs of proteins undoubtedly play a vital role in tumor cells, affecting both histones and non-histone proteins, covering modifications such as lactylation, crotonylation, acetylation, palmitoylation, and succinylation. Therefore, this review aims to elaborate on the abnormal levels of some major metabolites, related metabolic pathways, and the latest protein acyl PTMs they mediate in tumor cells, providing new insights for diagnosis and therapy in the field of oncology.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"247"},"PeriodicalIF":6.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118930","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}

{"title":"SOX4 reprograms fatty acid metabolism through the CHREBP to inhibit ferroptosis in hepatocellular carcinoma.","authors":"Fan Zhang, Zhiwei Wu, Yang Xiang, Qing He, Wanqing Li, Kaipeng Yang, Yijun Yang","doi":"10.1038/s41420-025-02527-4","DOIUrl":"10.1038/s41420-025-02527-4","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by aggressive progression and poor prognosis. Pathological angiogenesis in HCC is closely linked to metabolic reprogramming, particularly concerning fatty acid metabolism. The interplay between fatty acid metabolism and ferroptosis, a type of cell death driven by lipid peroxidation, is emerging as a crucial area of study. The transcription factor SOX4 is known to be overexpressed in various cancers, including HCC, and may play a key role in these processes. We assessed SOX4 expression in HCC using clinical samples and data from online databases. Next-generation RNA sequencing was employed to explore the effects of SOX4 on fatty acid metabolism, focusing on the CHREBP pathway. Functional assays, including lipid peroxidation and angiogenesis studies, were conducted to investigate the role of SOX4 in regulating ferroptosis and angiogenesis in HCC. SOX4 was found to be significantly upregulated in HCC and associated with enhanced angiogenesis. Mechanistically, SOX4 activated the CHREBP/SCD1 pathway, leading to increased production of monounsaturated fatty acids, which in turn inhibited ferroptosis. This suppression of ferroptosis contributed to the promotion of angiogenesis and tumor progression in HCC. In conclusion, SOX4 reprograms fatty acid metabolism via the CHREBP/SCD1 pathway, thereby inhibiting ferroptosis and promoting angiogenesis in HCC. These findings suggest that targeting the SOX4-CHREBP axis could represent a novel therapeutic strategy for HCC.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"246"},"PeriodicalIF":6.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118937","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}

{"title":"Androgen receptor inhibition sensitizes glioblastoma stem cells to temozolomide by the miR-1/miR-26a-1/miR-487b signature mediated WT1 and FOXA1 silencing.","authors":"Ana Belén Díaz Méndez, Marta Di Giuliani, Andrea Sacconi, Elisa Tremante, Valentina Lulli, Marta Di Martile, Giulia Vari, Francesca De Bacco, Carla Boccaccio, Giulia Regazzo, Maria Giulia Rizzo","doi":"10.1038/s41420-025-02517-6","DOIUrl":"10.1038/s41420-025-02517-6","url":null,"abstract":"<p><p>Glioblastomas (GBMs) are aggressive brain tumors and challenging cancers for diagnosis and treatment. Therapeutic options include surgery followed by chemotherapy with the DNA alkylator temozolomide (TMZ) and radiotherapy. However, the patient's prognosis remains poor due to tumor heterogeneity, cell infiltration and intrinsic or acquired resistance to therapy. Understanding the resistance mechanisms together with identifying new biomarkers are crucial for developing novel therapeutic strategies. MiRNAs play an important role in the biology of gliomas, they modulate tumorigenesis and therapy response. We recently identified the diagnostic/prognostic miR-1-3p, miR-26a-1-3p and miR-487b-3p signature that displays an oncosuppressive role on several glioma biological functions. In this study, we investigated the effects of the therapeutic potential of this three-miRNA signature as a regulator of response to TMZ. We found that ectopic expression of the miRNA signature in patient-derived GBM neurospheres treated with TMZ impaired cell proliferation and viability by necroptosis induction. Moreover, we identified WT1 and FOXA1, two transcription factors specifically involved in TMZ resistance, as novel direct targets of the miRNA signature. Of note, the repression of WT1 and FOXA1, elicited by the signature, caused a downregulation of the Androgen Receptor (AR) expression, an impairment of tumor-spheroid formation and reversed cancer cell stemness. These results were recapitulated using the AR inhibitor enzalutamide, confirming the involvement of the AR pathway. Our data indicate that the miR-1-3p/miR-26a-1-3p/miR-487b-3p signature, which has an impact on treatment response and cell stemness, may pave the way for miRNA-based complementary therapies in GBM patients.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"248"},"PeriodicalIF":6.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118932","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}

{"title":"miR-139-5p activates ferroptosis by inhibiting the expression of HMG-CoA reductase to inhibit the progression of glioma.","authors":"Zhongsheng You, Fei Wu, Yaofeng Zheng, Hongling Yang, Jianbo Ye, Hongyi Cai, Chuangcai Luo, Yang Liu, Yiquan Ke, Xiangdong Xu","doi":"10.1038/s41420-025-02532-7","DOIUrl":"10.1038/s41420-025-02532-7","url":null,"abstract":"<p><p>Glioma is the most aggressive and common tumour in the central nervous system. It has been reported that miR-139-5p plays an important role in regulating tumour progression. However, whether miR-139-5p affects the progression of glioma and the specific mechanism remains to be explored. Through experiments involving down-regulation or overexpression of miR-139-5p and treatment with simvastatin (SIM), qRT-PCR and Western Blot were used to detect the expression levels of related genes. Transmission electron microscopy (TEM) and corresponding kits were used to detect the changes in ferroptosis and cholesterol content in glioma cells. RNA-seq analysis was used to explore the specific mechanism by which miR-139-5p regulates ferroptosis. Our results demonstrate that miR-139-5p expression is significantly reduced in glioma cells compared to normal glial cells and is associated with poor prognosis. Overexpression of miR-139-5p promotes ferroptosis and inhibits tumour cell proliferation by downregulating HMG-CoA reductase (HMGCR) expression, consequently hindering glioma progression. Additionally, we found a synergistic effect between miR-139-5p overexpression and SIM treatment in promoting ferroptosis in gliomas. These findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with SIM. This study demonstrated that miR-139-5p promoted ferroptosis in glioma cells by down-regulating HMGCR expression and cholesterol synthesis. Moreover, miR-139-5p and SIM had a synergistic effect in promoting ferroptosis to prevent glioma progression.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"245"},"PeriodicalIF":6.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118936","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}

{"title":"Decoding the impact of MMP1+ malignant subsets on tumor-immune interactions: insights from single-cell and spatial transcriptomics.","authors":"Da-Ming Xu, Ling-Xiao Chen, Ting Xue, Xiao-Yu Zhuang, Li-Chao Wei, Hui Han, Miao Mo","doi":"10.1038/s41420-025-02503-y","DOIUrl":"10.1038/s41420-025-02503-y","url":null,"abstract":"<p><p>Matrix metalloproteinase 1 plays a pivotal role in tumor biology and immune modulation through its enzymatic remodeling of the extracellular matrix, facilitating tumor progression. In this study, we utilized large-scale single-cell RNA sequencing and spatial transcriptomics to investigate MMP1 expression, its cellular localization, and its impact on tumor progression and immune modulation. Our findings reveal that MMP1 expression is elevated in various tumor types and is strongly correlated with metastatic potential. High MMP1 expression was associated with increased activity in epithelial-mesenchymal transition signaling and TNFα/NF-κB pathways, which are known to promote tumor progression. Furthermore, MMP1+ malignant cells exhibited significant interactions with immune cells, particularly macrophages and CD8+ T cells. MMP1 expression correlated with enhanced macrophage infiltration and impaired CD8+ T-cell function, contributing to an immunosuppressive tumor microenvironment. Notably, the CXCL16-CXCR6 and ANXA1-FPR3 signaling axes were identified as key mediators of these interactions. Inhibition of MMP1 in vitro demonstrated reduced cell invasion, stemness, and proliferation, while increasing reactive oxygen species levels and promoting apoptosis. Our findings position MMP1 as a key player in the \"tumor-immune\" vicious cycle and a promising therapeutic target to enhance anti-tumor responses and improve patient outcomes.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"244"},"PeriodicalIF":6.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109939","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}