Cell Biology and Toxicology最新文献

{"title":"Correction to: Chronic cadmium exposure promotes TRPM7‑dependent acquisition of a myofibroblast‑like phenotype in pancreatic stellate cells.","authors":"Mathilde Fourgeaud, Julie Auwercx, Alexis Lalot, Laure Noé, Belinda Duchêne, Anthony Verdin, Sara Agrane, Frédéric Hague, Stéphanie Guénin, Nour Jaber, Aurélie Dupont-Deshorgue, Laurent Gutierrez, Denis Chatelain, Frédéric Ledoux, Isabelle Dhennin-Duthille, Bertrand Brassart, Sylvie Brassart-Pasco, Nicolas Jonckheere, Mathieu Gautier","doi":"10.1007/s10565-026-10289-7","DOIUrl":"10.1007/s10565-026-10289-7","url":null,"abstract":"","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"42 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma.","authors":"Jinxiang Zhu, Longwei Guo, Hao Dai, Zhiwei Zheng, Jinfeng Yan, Junsong Liu, Shaoqiang Zhang, Xiang Li, Xin Sun, Qian Zhao, Chongwen Xu","doi":"10.1007/s10565-026-10253-5","DOIUrl":"10.1007/s10565-026-10253-5","url":null,"abstract":"","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"42 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: MiR-337-3p confers protective effect on facet joint osteoarthritis by targeting SKP2 to inhibit DUSP1 ubiquitination and inactivate MAPK pathway.","authors":"Shengsheng Jian, Dixin Luo, Yeyang Wang, Wangyang Xu, Hui Zhang, Li Zhang, Xiaozhong Zhou","doi":"10.1007/s10565-026-10231-x","DOIUrl":"10.1007/s10565-026-10231-x","url":null,"abstract":"","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"42 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of synergistic action between olaparib and KPT-330 in pancreatic cancer.","authors":"Yuntao Yang, Yuying Zhang, Yajing Zhang, Hang Su, Huixiang Dong, Xiaohan Jin, Shiqiang Tai, Zhengchao Shen, Zhiyuan Chen, Hao Xie, Da Fu, JiaBin Jin, Xiaoming Wang","doi":"10.1007/s10565-026-10219-7","DOIUrl":"10.1007/s10565-026-10219-7","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and prognostically poor cancer driven by multifaceted mechanisms, notably immune evasion and drug resistance. The majority of PDAC patients present with unresectable locally advanced or metastatic disease, emphasizing a critical unmet need for effective therapies against advanced-stage pancreatic cancer. Despite the proven efficacy of the PARP inhibitor Olaparib against pancreatic cancer in patients carrying BRCA mutations, its practical use is limited by the development of acquired resistance. The clinical application of the PARP inhibitor Olaparib is limited by acquired resistance, making combination therapy a promising strategy to improve treatment responses. Exportin 1 (XPO1) is frequently overexpressed in PDAC cells, representing a therapeutic target, and its inhibitor KPT-330 has demonstrated antitumour potential. Therefore, we aim to combine Olaparib with KPT-330 to enhance its therapeutic effect against PDAC.</p><p><strong>Objective: </strong>This study aimed to investigate the synergistic antitumour effects of the combination of Olaparib and KPT-330 against PDAC and to elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>We applied RNA sequencing to pancreatic cancer cell lines following combination therapy to identify differentially expressed genes. Separately, Western blotting was performed to measure both the expression and phosphorylation status of key proteins within the involved signaling cascades.</p><p><strong>Results: </strong>The combination of KPT-330 and Olaparib significantly suppressed PDAC cell viability and tumour growth. Mechanistic investigation revealed that the combination specifically reduced SGPP2 levels, leading to inhibition of the IL-6/JAK2/STAT3 signaling axis. Evidence included diminished p-JAK2 and p-STAT3, with no alteration in total JAK2 or STAT3. This SGPP2-associated synergistic effect may overcome olaparib resistance by modulating the immunosuppressive tumor microenvironment.</p><p><strong>Conclusion: </strong>This study reveals that the combination of Olaparib and KPT-330 enhances antitumor efficacy in pancreatic cancer by downregulating SGPP2, a tumor-associated protein, thereby inhibiting the IL-6/JAK2/STAT3 signaling pathway. SGPP2 is proposed as a key molecular node linking the two agents. Collectively, these findings provide preclinical evidence that the Olaparib and KPT-330 combination acts synergistically via the SGPP2/STAT3 axis, supporting its potential application in pancreatic cancer combination therapy.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE2C at the crossroads of cell cycle regulation and DNA damage response in cancer.","authors":"Sayandrila Paul, Amoolya Kandettu, Sanjiban Chakrabarty","doi":"10.1007/s10565-026-10230-y","DOIUrl":"10.1007/s10565-026-10230-y","url":null,"abstract":"<p><p>The ubiquitin-proteasome system (UPS) is an important regulator of numerous cellular pathways, including DNA repair, protein degradation, the cell cycle, and signal transduction. UBE2C, a member of the ubiquitin-conjugating enzyme family, facilitates the ubiquitination of essential cellular regulators. Notably, UBE2C is consistently overexpressed in breast, lung, brain, hepatocellular, and ovarian carcinomas. Increased UBE2C expression is associated with tumour aggressiveness, genomic instability, epithelial-to-mesenchymal transition, and resistance to chemotherapy and radiotherapy. Our review explores the mechanistic involvement of UBE2C in diverse cancers, with a particular focus on its involvement in DNA damage repair mediated by the anaphase-promoting complex (APC/C). Furthermore, the regulatory effects of miR-381, miR-503, and miR-205 on UBE2C expression were examined, highlighting the promising prospects of these miRNAs for targeted cancer therapy. The involvement of UBE2C in different cancer hallmarks underscores its potential as a biomarker and therapeutic target. A comprehensive understanding of its mechanistic involvement in cell cycle regulation and DNA repair will further enhance its application in diagnostics, personalised medicine, and precision medicine.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functions, mechanisms and clinical relevance of RNA and protein acetyltransferase NAT10: a comprehensive review.","authors":"Chengyu Zhang, Jinmeng Lu, Lu Tang, Huili You, Mengshuang Yin, Ying Gong, Jing Wu, Chao Xiong, Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, Shuai Deng, Yueshui Zhao, Meijuan Chen, Wanping Li, Xiaobing Li, Yuhong Sun, Li Gu, Fang Wang, Zhangang Xiao, Jing Shen","doi":"10.1007/s10565-026-10227-7","DOIUrl":"10.1007/s10565-026-10227-7","url":null,"abstract":"<p><p>The rapid advances in epigenetic and epitranscriptomic regulatory mechanisms have opened new prospects for precision therapies in various diseases. N-acetyltransferase 10 (NAT10) is currently the only known eukaryotic RNA ac4C acetyltransferase and has also been reported to acetylate multiple protein substrates, regulating diverse physiological processes. In this review, we comprehensively describe the domain organization, structural features and subcellular localization of NAT10. The molecular mechanisms underlying NAT10-mediated RNA ac4C modification and protein acetylation, as well as their biological functions across physiological and pathological contexts, are systematically summarized, with the aim of facilitating its clinical translation. Furthermore, we review the recent advances in NAT10-targeted therapeutic strategies, discuss the potential for combining NAT10-targeted strategies with existing treatment modalities, and propose possible approaches for optimization. By integrating current evidence, this review provides insights into the functions of NAT10 and highlights future research directions for its validation and translational development as a clinical therapeutic target in various diseases.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIK3CB depletion restores immunosurveillance and enhances radioactive iodine response in hepatocellular carcinoma.","authors":"Yuanren Gao, A Rouhan, Wenbo Wang, Tengchuang Ma, Yali Cui","doi":"10.1007/s10565-026-10229-5","DOIUrl":"10.1007/s10565-026-10229-5","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite the existence of various treatments, including iodine-125 (¹²⁵I) seed implantation. Nevertheless, resistance to these treatments persists as a challenge. Here, we identified PIK3CB as a key molecule involved in the nonresponse to ¹²⁵I and immune evasion in HCC and expounded its upstream modifiers. Differentially expressed genes in HCC tissues of ¹²⁵I non-responders or responders were screened using transcriptomics sequencing. PIK3CB expression was increased in the tumors of HCC ¹²⁵I non-responders. PIK3CB knockout increased HCC cell response to ¹²⁵I and inhibited tumor growth. PIK3CB induced PD-L1 expression to support the evasion of HCC cells from CD8⁺ T cells and NK cells-mediated immunosurveillance. The binding of ZBED4 at the PIK3CB promoter induced transcription of PIK3CB, and the knockout of ZBED4 enhanced the ¹²⁵I response and inhibited the immune evasion of HCC cells. Overexpression of ASB2 enabled ubiquitination of ZBED4. ASB2 overexpression increased ¹²⁵I sensitivity and inhibited immune evasion in HCC, which was reversed by overexpression of ZBED4 or PIK3CB. Consequently, these findings offer significant insights into the ASB2/ZBED4/PIK3CB regulatory axis, illuminating the potential for enhancing the efficacy of immune checkpoint blockade and ¹²⁵I seed brachytherapy in HCC treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-exposure to polystyrene nanoparticles and tetrabromobisphenol A induces genotoxicity and interferes with intestinal barrier differentiation.","authors":"Patricia Soto-Bielicka, Soledad Sanz-Alférez, M José Hazen, Paloma Fernández Freire, Ana Peropadre","doi":"10.1007/s10565-026-10228-6","DOIUrl":"10.1007/s10565-026-10228-6","url":null,"abstract":"<p><p>Tetrabromobisphenol A (TBBPA) and polystyrene nanoparticles (PSNPs) are contaminants of emerging concern frequently detected in environmental matrices, with dietary exposure representing a major route. Despite their co-occurrence, data on combined toxicity remain limited. This study evaluated the effects of TBBPA and PSNPs individual and combined exposure on human intestinal barrier integrity, differentiation and function using differentiated Caco-2 cells and Caco-2/HT29-MTX co-cultures as validated in vitro models of increasing complexity. Cells were exposed to TBBPA (1-150 µM) and PSNPs (0.1-50 µg/mL) individually or in combination, either for 24 h in fully differentiated monolayers or continuously during the 21-day differentiation period. In differentiated Caco-2 cells, combined exposure altered cytoskeletal organization, with PSNPs being internalized and accumulating as large intracellular aggregates that persisted for at least 144 h post-exposure. Ultrastructural analysis revealed microvilli alterations and multilamellar bodies formation, although tight junction architecture remained intact and cellular adhesion structures recovered progressively following contaminant removal, suggesting retained barrier repair capacity. During the differentiation period, TBBPA was the primary cytotoxic agent and PSNPs alone showed no cytotoxicity at the concentrations tested, as confirmed by benchmark dose analysis, which yielded low relative potency factor values for PSNPs across all tested combinations. Genotoxicity assessment revealed oxidative DNA damage in selected TBBPA and PSNPs combinations using the FPG-modified comet assay, with gene expression analysis indicating activation of DNA damage response and oxidative stress pathways. Co-exposure modulated the expression of intestinal differentiation markers, including ALPI, suggesting interference with epithelial maturation processes. The complexity of the dose-response relationships observed underscores the importance of comprehensive dose-range testing and the use of physiologically relevant differentiated models in the risk assessment of contaminant mixtures.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation-driven stabilization of the S100A11/ANXA2 complex promotes pancreatic cancer metastasis.","authors":"Bo Zheng, Lijun Cai, Ying Deng, Lan Yang","doi":"10.1007/s10565-026-10225-9","DOIUrl":"10.1007/s10565-026-10225-9","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced Warburg effect and high lactate levels. While lysine lactylation (Kla) is an emerging post-translational modification, its role in regulating the S100A11/ANXA2 complex-a critical driver of membrane repair and metastasis-remains unexplored. In this study, we identified that S100A11 (K3, K55) and ANXA2 (K49) are significantly lactylated in PDAC tissues. Lactate-induced lactylation of S100A11 at K3 and K55 inhibits FBXW11-mediated ubiquitination and proteasomal degradation, thereby stabilizing the protein. This stabilized S100A11 subsequently shields ANXA2 from TRIM21-mediated degradation. Reciprocally, lactylation of ANXA2 at K49 enhances its capacity to recruit S100A11 to the plasma membrane. Functional assays demonstrated that this lactylation-driven interdependent regulatory axis promotes PDAC cell migration, invasion, and metastasis both in vitro and in vivo. Clinical analysis of TCGA data revealed that low expression of both S100A11 and ANXA2 predicts significantly improved progression-free and overall survival in PDAC patients. In summary, our findings establish a novel link between metabolic reprogramming and the post-translational regulation of the membrane repair machinery. Lactylation of the S100A11/ANXA2 axis is a key driver of PDAC progression and serves as a promising prognostic biomarker and potential therapeutic target.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.","authors":"Chenhao Zhao, Liang Kang, Jiaqi Wang, Yanxin Wang, Yu Chen, Luping Zhou, Chongyu Jia, Huaqing Zhang, Jingyu Zhang, Zhiwei Chen, Renjie Zhang, Cailiang Shen","doi":"10.1007/s10565-026-10226-8","DOIUrl":"10.1007/s10565-026-10226-8","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc (IVD) degeneration (IDD) is a leading cause of low back pain, with limited treatment options. The degenerative disc's harsh microenvironment promotes nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) death and hinders self repair. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an atypical neurotrophic factor, has protective effects in degenerative diseases. However, its role in IDD is unclear.</p><p><strong>Methods: </strong>Assessment of MANF expression was conducted in both human nucleus pulposus tissues and a rat IVD puncture model. An in vitro model of degeneration was established by acid treatment of NP-MSCs, and the functional role of MANF was explored through its knockdown and overexpression. RNA sequencing was employed to identify downstream targets. The therapeutic potential of MANF-overexpressing NP-MSCs was evaluated in a rat puncture model.</p><p><strong>Results: </strong>MANF expression was markedly downregulated in degenerated IVD tissues from both human patients and rat models. Correspondingly, in vitro experiments demonstrated that MANF knockdown exacerbated, while its overexpression mitigated, acid-induced apoptosis of NP-MSCs. Mechanistically, MANF attenuated mitochondrial dysfunction and ER stress of NP-MSCs under acidic conditions by maintaining MAM integrity, as demonstrated by the complete abolition of this protection upon treatment with the MAM uncoupler FATE1. Transcriptomic analysis and subsequent validation identified receptor expression-enhancing protein 1 (REEP1) as a critical downstream effector through which MANF safeguards MAM integrity. We further elucidated that MANF upregulates REEP1 expression by directly inhibiting miR-33b-5p. In vivo, transplantation of MANF-overexpressing NP-MSCs effectively attenuated IDD in a rat model.</p><p><strong>Conclusion: </strong>MANF protected NP-MSCs from acidosis by sustaining MAM integrity via the MiR-33b-5p/REEP1 axis. These findings reveal MANF's mechanism and therapeutic potential for IDD.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}