Cancer Cell International最新文献

{"title":"Venetoclax synergizes with Wnt/β-catenin inhibitor C-82 in acute myeloid leukemia by increasing the degradation of Mcl-1 protein.","authors":"Mengya Pan, Changqing Jiao, Menghua Sun, Duo Jin, Yin Wang, Haoxuan Wu, Yan Zhang, Enbo Chen, Bobin Su, Junjie Zhou, Xiaoying Liu, Jian Ge","doi":"10.1186/s12935-025-03825-8","DOIUrl":"https://doi.org/10.1186/s12935-025-03825-8","url":null,"abstract":"<p><strong>Background: </strong>Due to compensatory survival signalling and overexpression of anti-apoptotic Bcl-2 family proteins, the majority of AML patients developed acquired resistance of venetoclax (VEN) to combination therapy of VEN with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs). Dysregulation of the Wnt/β-catenin signalling pathway is intently associated with leukemia development and chemotherapy resistance. However, there is currently no Wnt/β-catenin inhibitor approved for clinical use and it is not clear whether targeting the Wnt/β-catenin pathway enhances the anti-leukemic activity of VEN.</p><p><strong>Methods: </strong>Analysis of the AML patient's data in the BeatAML and GEO databases. Establishing the MOLM13 venetoclax-resistant cell line (MOLM13-R cells) based on the MOLM13 parental cell line. CCK-8, Annexin-V/PI and Western blotting were performed to assess the effects of the combination of Wnt/β-catenin inhibitor C-82 and VEN in AML cell lines. The potential mechanisms of synergistic effects of the two-drug combination were explored by Western blotting and ubiquitination immunoprecipitation.</p><p><strong>Results: </strong>We displayed that the expression of β-catenin abnormally upregulated in AML patients and MOLM13-R cells. Knockdown of β-catenin could increase cell apoptosis in MOLM13-R cells. Combined treatment of C-82 with VEN synergistically inhibited AML cell growth and increased apoptosis. Mechanistically, C-82 disrupted the stability of Mcl-1 protein, and Mcl-1 downregulation was associated with different phosphorylation sites of Mcl-1 and proteasomal degradation. The combination of C-82 and VEN synergistically induced concurrent mitochondrial-associated apoptosis and gasdermin E (GSDME)-dependent pyroptosis.</p><p><strong>Conclusion: </strong>Our findings propose an effective treatment strategy for AML patients through the combination of C-82 and VEN, positioning this regimen as a promising therapeutic option.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"197"},"PeriodicalIF":5.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocellular carcinoma drug resistance models.","authors":"Xiaolu Xie, Yaomin Wang, Ziyi Wang, Lei Zhang, Jun Li, Yaling Li","doi":"10.1186/s12935-025-03821-y","DOIUrl":"10.1186/s12935-025-03821-y","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Although drug therapy has been well developed and applied, its clinical efficacy is limited due to primary or acquired drug resistance in most HCC patients. Therefore, it is of great clinical significance to elucidate the key molecular mechanisms of resistance and improve the sensitivity of HCC cells to drugs. At present, a variety of HCC drug resistance models have been developed to find out resistance mechanisms, screen biomarkers, and explore strategies to reverse drug resistance, including traditional HCC drug resistance models, HCC patient-derived drug resistance models, three-dimensional drug resistance models, transgenic drug resistance models, and multi-drug resistance models. Here, we searched PubMed, Embase and Web of science for studies related to HCC drug resistance models in recent years, systematically summarized the established methods and characteristics of these models, reviewed their applications and compared their advantages and disadvantages, aiming to provide reference for the selection of appropriate models for HCC drug resistance research.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"195"},"PeriodicalIF":5.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172829","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":"Immunoprevention of non-viral cancers: challenges and strategies for early intervention.","authors":"Kajal Biswas, Lillian S Kuo, Robert H Shoemaker, Altaf Mohammed","doi":"10.1186/s12935-025-03817-8","DOIUrl":"10.1186/s12935-025-03817-8","url":null,"abstract":"<p><p>While the effects of cancer vaccines have been extensively studied in the therapeutic setting, research has been more limited in the areas of cancer prevention and interception. Although cancer prevention by vaccines has been possible for viral-mediated cancers, such as cervical cancers and hepatocellular carcinoma, preventing non-viral cancers by immunopreventive vaccines is challenging. Many tumors at late stages are less responsive to treatments, including immunotherapies and vaccines, in part due to an immunosuppressive microenvironment. Shifting the strategy to intervention at early stages of cancer development and progression and focusing on high-risk cohorts with defined molecular targets offers a pathway for improved vaccine efficacy. Current research on the role of immune mechanisms during tumor initiation and progression is rapidly evolving and recent emerging preclinical immunoprevention studies have shown that vaccines can induce host immune response and effectively control tumor onset and progression. In this review, we address important considerations and challenges regarding the development of cancer immunoprevention for non-viral cancers. We also discuss significant, innovative, and impactful preclinical and clinical immunoprevention studies in various cancers. This includes neoantigen discovery, the use and optimization of immunomodulating agents either alone or in combination with vaccines, and strategies for optimizing vaccines. We conclude by discussing prospects for immunoprevention research and potential opportunities to advance the field in the future.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"196"},"PeriodicalIF":5.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172831","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":"Revealing a novel Decorin-expressing tumor stromal subset in hepatocellular carcinoma via integrative analysis single-cell RNA sequencing.","authors":"Chi Hsiao, Wen-Chieh Liao, Ju-Pi Li, Yu-Cheng Chou, Yu-Lun Chou, Jeng-Rong Lin, Chia-Hua Chen, Chiung-Hui Liu","doi":"10.1186/s12935-025-03811-0","DOIUrl":"10.1186/s12935-025-03811-0","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, emphasizing the need for novel therapeutic strategies. Decorin (DCN), a chondroitin sulfate proteoglycan (CSPG), has been proposed as a tumor suppressor, yet its precise role in HCC and the tumor microenvironment (TME) remains underexplored. Through integrated analyses of bulk RNA and single-cell RNA sequencing datasets, we identified a distinct tumor stromal subset highly expressing DCN and associated chondroitin sulfate (CS) synthases. Our findings revealed that DCN expression is significantly downregulated in HCC tissue, but upregulated in peri-tumor stroma, where it correlates with better prognosis and reduced capsular invasion. Western blot analysis demonstrated that CS-DCN, the glycosylated form of DCN, plays a dominant role in this context. Single-cell clustering analysis identified a unique stromal subset in HCC characterized by elevated expression of DCN, CSPGs, and CS synthases, associated with extracellular matrix (ECM) remodeling and protective barrier functions. A six-gene DCN-associated signature derived from this subset, including DCN, BGN, SRPX, CHSY3, CHST3, and CHPF, was validated as a prognostic marker for HCC. Furthermore, functional assays demonstrated that CS-DCN significantly inhibited HCC cell proliferation and invasion. Our study highlights the critical role of DCN in HCC TME and provides insights into its therapeutic potential. Modulating CSPG pathways, particularly on CS-DCN-expressing stromal cells, may offer a promising approach for improving HCC treatment and patient outcomes.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"194"},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149593","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":"Transforming bone cancer treatment: a comprehensive review of green-synthesized metal nanoparticles.","authors":"Linying Xia, Chao Zhou, Xiankun Liu, Yijun Yu, Qiong Xie, Hongming Lin, Xiaochun Xiong, Songou Zhang, Wenqing Liang, Haiyan Shao","doi":"10.1186/s12935-025-03827-6","DOIUrl":"10.1186/s12935-025-03827-6","url":null,"abstract":"<p><p>Osteosarcoma (OS), chondrosarcoma (CHS), and Ewing sarcoma (EWS) are the main types of bone cancer (BC). OS is the most common BC in this group. It is most common in children and older people, especially in their long bones. Treatments for bone sarcomas and tumors have slowly improved, so researchers began looking into additional and alternative approaches to standard therapies. Therefore, the ability to precisely manipulate metallic nanoparticles (MNPs)' form, size, charge, and surface modification makes them very useful in treating bone cancer. However, due to the biocompatibility and possible toxicity of MNPs, MNP has limits for clinical use in treating BC. Therefore, the green synthesis of MNPs is achieved by bio-reducing metallic ions, which results in the creation of NPs, using living entities or their extracts. Green MNPs derived from natural sources provide a secure and environmentally responsible solution. Benefits of green MNPs include tailored medicine delivery and biocompatibility. Green MNPs reduce damage to healthy cells while improving the targeting of bone cancer cells. In this study, we reviewed how different MNPs synthesized using green methods can help treat various types of BC. This work reviewed the usual way of making MNPs for treating BC, the problems with this standard way of making MNPs, and the benefits and possible future uses of green synthetic MNPs for treating BC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"193"},"PeriodicalIF":5.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141506","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":"LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression.","authors":"Yanfang Liu, Yuanjun Zeng, Sikai Wang, Jiangyan Chen, Zhouqi Wang, Yang Zhao, Kuiyu Gong, Guihua Wang","doi":"10.1186/s12935-025-03812-z","DOIUrl":"10.1186/s12935-025-03812-z","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based chemotherapy is the standard first-line cancer treatment. However, patients experience relapses due to chemoresistance. We found that long non-coding RNA 16 (lncRNA16) promotes platinum resistance and inhibits cell death in non-small cell lung cancer (NSCLC). However, the type of cell death inhibited by lncRNA16 remains unknown.</p><p><strong>Methods: </strong>The biological roles of lncRNA16 and microRNA 1827 (miRNA1827) in cell proliferation and colony formation were determined using functional experiments. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to confirm the interactions between lncRNA16 and miRNA1827. In vivo patient-derived tumor xenograft (PDX) models were used to investigate the effects of miRNA1827 agomir on platinum resistance.</p><p><strong>Results: </strong>Pyroptosis was inhibited in platinum-resistant NSCLC cells. LncRNA16 contributed to the expression of methyl-CpG binding domain protein 3 (MBD3) by sponging miRNA1827, thereby inhibiting gasdermin E (GSDME) expression, which inhibited pyroptosis in platinum-resistant NSCLC. The miRNA1827 agomir repressed platinum resistance in vitro experiments and in vivo PDX models.</p><p><strong>Conclusion: </strong>We identified a novel function of lncRNA16 in inhibiting pyroptosis and proposed an effective therapeutic drug, the miRNA1827 agomir, for chemosensitization. This study offers a potential strategy for treating patients with NSCLC, especially those with platinum resistance.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"192"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141496","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":"EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.","authors":"Nozomi Hirai, Sho Tamai, Toshiya Ichinose, Hemragul Sabit, Norihiko Saito, Satoshi Iwabuchi, Mitsutoshi Nakada","doi":"10.1186/s12935-025-03826-7","DOIUrl":"10.1186/s12935-025-03826-7","url":null,"abstract":"<p><strong>Background: </strong>EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.</p><p><strong>Methods: </strong>EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.</p><p><strong>Results: </strong>QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.</p><p><strong>Conclusion: </strong>EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"191"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141363","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":"Targeting PIK3CB/YAP1 improves the sensitivity of paclitaxel by suppressing aging in head and neck squamous tumor cells.","authors":"Junzhi Liu, Huimin Li, Ruotong Sun, Guoguang Ying, Zheng Liang","doi":"10.1186/s12935-025-03818-7","DOIUrl":"10.1186/s12935-025-03818-7","url":null,"abstract":"<p><strong>Background: </strong>Tumor cell senescence reduces sensitivity to anticancer drugs, making senescent cell elimination an ideal strategy to enhance chemotherapy sensitivity. The interaction between the PI3K/Akt and Hippo/YAP1 pathways is increasingly studied, but the role of PIK3CB, YAP1, and their impact on senescence and chemotherapy sensitivity in head and neck tumors is unclear.</p><p><strong>Methods: </strong>Public datasets (GEO, TCGA, HPA) were analyzed for PIK3CB expression and clinical associations. Immunohistochemistry, cell proliferation assays, DNA replication, colony formation, aging markers, and DNA damage assessments were conducted. Bulk and single-cell transcriptomics and proteomics data were analyzed. Cell passage effects on aging and the impact of PIK3CB modulation on YAP1 were evaluated. Potential drugs targeting PIK3CB were identified, and the effects of senescent cell clearance drugs on clonogenic abilities and chemotherapy sensitivity were assessed.</p><p><strong>Results: </strong>Elevated PIK3CB expression in HNSCC tumors correlated with advanced stages, older age, and decreased survival. PIK3CB and YAP1 expressions were strongly correlated, impacting aging pathways and cellular proliferation. Modulation of PIK3CB affected tumor cell proliferation, aging, and DNA damage. The combined application of navitoclax and paclitaxel can reduce tumor cell proliferation and autonomous migration ability, influenced by the levels of PIK3CB.</p><p><strong>Conclusion: </strong>High PIK3CB expression in head and neck cancers is linked to poor prognosis and advanced tumor grades. PIK3CB promotes cell proliferation and reduces aging via the YAP1 pathway. The combination of navitoclax and paclitaxel reduces tumor cell proliferation and autonomous migration ability, providing a basis for further exploration of increasing chemotherapy sensitivity.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"190"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141500","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":"UFUR maintenance therapy significantly improves survival in locally advanced head and neck squamous cell carcinoma following definitive chemoradiotherapy.","authors":"Jason Chia-Hsun Hsieh, Ming-Yu Lien, Pei-Hung Chang, Hung-Ming Wang, Kun-Yun Yeh, Ching-Liang Ho, Ching-Yun Hsieh, Meng-Che Hsieh, Jia-Hong Chen","doi":"10.1186/s12935-025-03807-w","DOIUrl":"10.1186/s12935-025-03807-w","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges, particularly in patients with advanced disease. Despite advancements in treatment, high recurrence rates and poor overall survival (OS) remain major concerns. This study evaluates the impact of tegafur-uracil (UFUR) maintenance therapy on survival outcomes in patients with advanced HNSCC following definitive chemoradiotherapy.</p><p><strong>Methods: </strong>A cohort of 424 advanced HNSCC patients treated with definitive chemoradiotherapy were analyzed, with a median follow-up of 25 months. Patients were stratified into UFUR (+) and UFUR (-) groups, with baseline characteristics balanced across both arms. Oncologic outcomes, including recurrence-free survival (RFS), OS, locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between these groups.</p><p><strong>Results: </strong>UFUR maintenance therapy significantly reduced recurrence rates (34% vs. 47%, p < 0.002), driven primarily by improving locoregional control (23% vs. 37%, p < 0.001). While distant metastasis rates were similar between groups, UFUR (+) patients demonstrated a markedly improved median OS (51.6 months vs. 24.3 months, p < 0.001). The UFUR (+) group also showed superior median LRFS (36.9 months vs. 20.2 months, p = 0.003) and DMFS (44.0 months vs. 23.5 months, p = 0.010). Subgroup analysis confirmed the benefits of UFUR maintenance across different stages of disease. Multivariate analysis identified UFUR maintenance, gender, and T stage as independent predictors of survival.</p><p><strong>Conclusion: </strong>UFUR maintenance therapy significantly improves survival outcomes in patients with advanced HNSCC following definitive chemoradiotherapy, particularly through enhanced locoregional control, and should be considered a key component of personalized treatment strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"187"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132067","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":"NCAPD3 contributes to lung cancer progression through modulated lactate-induced histone lactylation and MEK/ERK/LDHA axis.","authors":"Zhibo Chang","doi":"10.1186/s12935-025-03814-x","DOIUrl":"10.1186/s12935-025-03814-x","url":null,"abstract":"<p><p>Lung cancer (LC) is one of the most common malignant tumors globally. Non-SMC condensin II complex subunit D3 (NCAPD3) has been involved in the progression of many kinds of tumors. However, the effects of NCAPD3 in LC remain unclear. NCAPD3 expression was investigated by the Ualcan database and using Western blot. The effect of NCAPD3 on prognosis was explored via the Kaplan-Meier plotter database. Cell viability, colony formation, apoptosis, and Transwell assays, and in vivo tumorigenesis were performed to reveal the biological roles of NCAPD3. Glycolysis was assessed via measurement of glucose consumption, extracellular acidification rate (ECAR), lactate production, and ATP levels. The deeper mechanisms of NCAPD3 were investigated by Western blot and rescue experiments. Upregulation of NCAPD3 levels in LC tissues was found in Ualcan and significantly associated with poor prognosis. The expression of NCAPD3 was up-regulated in LC cell lines compared to BEAS-2B cells. Knockdown and overexpression experiments suggested that proliferation, apoptosis, migration, invasion, and glycolysis were regulated by NCAPD3 via the MEK/ERK/LDHA pathway. Additionally, NCAPD3 knockdown inhibited tumor growth in vivo. Mechanistically, NCAPD3 overexpression-mediated activation of the MEK/ERK/LDHA pathway and proliferation, Glucose uptake, and glycolysis were attenuated by MEK inhibitor U0126. Also, histone lactylation helps in tumorigenesis by promoting NCAPD3 expression. Taken together, our results revealed that histone lactylation of NCAPD3 promoted proliferation, migration, invasion, and glycolysis through modulating the MEK/ERK/LDHA signaling pathway in LC, which highlights a novel understanding of NCAPD3 in LC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"189"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132066","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}