Cell Division最新文献

{"title":"FGF4 drives tumor progression in triple-negative breast cancer via IL6/STAT3-mediated macrophage M2 polarization and immune suppression.","authors":"Xuanhe Zhang, Shushan Zhang, Yuanyuan Han","doi":"10.1186/s13008-025-00164-y","DOIUrl":"10.1186/s13008-025-00164-y","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates how Fibroblast Growth Factor 4 (FGF4) drives triple-negative breast cancer (TNBC) progression by modulating macrophage polarization through the IL6/STAT3 signaling axis, with a focus on immune suppression and tumor microenvironment remodeling.</p><p><strong>Methods: </strong>TNBC transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify FGF4-associated pathways using differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and immune infiltration profiling via Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Functional annotations (GO/KEGG) highlighted IL6/STAT3 as a key pathway. In vitro models with FGF4-overexpressing or knockdown TNBC cells were co-cultured with macrophages to assess IL6/STAT3 activation, M2 polarization markers (CD206, Arg1), and cytokine secretion (ELISA). Tumor cell behaviors (proliferation, migration, invasion) were quantified. In vivo orthotopic TNBC models in mice evaluated FGF4's impact on tumor growth, immune cell infiltration (flow cytometry), and STAT3 activity (Western blot).</p><p><strong>Results: </strong>FGF4 was upregulated in TNBC and strongly correlated with M2 macrophage infiltration. In vitro, FGF4 activated IL6/STAT3 signaling, inducing macrophage polarization to an M2 phenotype with elevated IL-10/TGF-βsecretion and suppression of T cell proliferation. Conditioned media from M2 macrophages enhanced TNBC cell aggressiveness. In vivo, FGF4-overexpressing tumors showed higher weight and increased M2 markers, whereas FGF4 knockdown reduced tumor volume and enhanced CD8⁺ T cell infiltration.</p><p><strong>Conclusion: </strong>FGF4 promotes TNBC progression by activating IL6/STAT3 to reprogram macrophages into immune-suppressive M2 effectors, fostering a tumor-permissive microenvironment. Targeting FGF4 may disrupt this crosstalk, offering a novel immunotherapeutic strategy for TNBC.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"22"},"PeriodicalIF":2.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: LncRNA NUTM2A-AS1 silencing inhibits glioma via miR-376a-3p/YAP1 axis.","authors":"Yuecheng Zeng, Zhenyu Yang, Yang Yang, Peng Wang","doi":"10.1186/s13008-025-00157-x","DOIUrl":"10.1186/s13008-025-00157-x","url":null,"abstract":"","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"21"},"PeriodicalIF":2.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMAD3 orchestrates RNF167 and STAMBPL1-mediated Sestrin2 ubiquitination to drive gastric cancer progression.","authors":"Ning Zhang, Na Zhao, Hainan Zhang, Le Yao, Hongtao Si","doi":"10.1186/s13008-025-00163-z","DOIUrl":"10.1186/s13008-025-00163-z","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) continues to pose a significant global health burden, necessitating a thorough understanding of the molecular mechanisms driving its progression. This study aimed to investigate the regulatory role of SMAD3 in modulating Sestrin2 ubiquitination stability and its implications in GC cell behaviors.</p><p><strong>Methods: </strong>Leveraging GC-related single-cell transcriptomic data, we employed advanced analytical approaches to unveil the relationship between SMAD3 and Sestrin2. Experimental validations involving RT-qPCR, Western blotting, and immunofluorescence analyses elucidated the impact of SMAD3 on Sestrin2 expression and subcellular localization. In vitro models of SMAD3 overexpression and knockdown were utilized to assess the functional consequences on GC cell proliferation, migration, invasion, and apoptosis. The interaction between SMAD3 and ubiquitination-related enzymes RNF167 and STAMBPL1 was investigated through immunoprecipitation assays.</p><p><strong>Results: </strong>Our findings revealed a positive correlation between SMAD3, Sestrin2, and STAMBPL1 expression, indicating a regulatory network within GC cells. SMAD3 was shown to stabilize Sestrin2 protein levels by influencing the ubiquitination processes of STAMBPL1 and RNF167. Functional assays demonstrated the promotion of GC cell proliferation, migration, and invasion, along with decreased apoptosis, by the SMAD3-Sestrin2 axis. Moreover, SMAD3-mediated regulation of Sestrin2 stability was found to enhance GC metastasis.</p><p><strong>Conclusion: </strong>The study underscores the critical role of SMAD3 in modulating Sestrin2 expression and stability, consequently impacting GC cell behaviors and metastatic potential. The SMAD3-Sestrin2 axis emerges as a promising therapeutic target for GC treatment.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"20"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFAP2A upregulates FAM83A to suppress ferroptosis and diminish cisplatin sensitivity in non-small cell lung cancer.","authors":"Qi Sun, Weifeng Qu, Ye Wang, Kejia Yang, Yuan Weng","doi":"10.1186/s13008-025-00162-0","DOIUrl":"10.1186/s13008-025-00162-0","url":null,"abstract":"<p><strong>Background: </strong>FAM83A plays a significant role in the development of non-small cell lung cancer (NSCLC). This study elucidated the biological role of FAM83A in ferroptosis and cisplatin (DDP) sensitivity in NSCLC cells.</p><p><strong>Methods: </strong>The expression patterns of FAM83A and TFAP2A were analyzed by bioinformatic analysis. mRNA and protein levels were detected by quantitative PCR, immunoblotting, and immunohistochemistry, respectively. Cell invasion, migration, and viability were assessed by transwell, wound healing, CCK-8 assays, respectively. Cell ferroptosis was evaluated by measuring the levels of ROS, Fe²⁺, MDA, GSH, and SOD. Chromatin immunoprecipitation (ChIP) and luciferase assays were used to confirm the relationship between TFAP2A and the FAM83A promoter. Xenograft models were generated to evaluate the role of TFAP2A in vivo.</p><p><strong>Results: </strong>FAM83A and TFAP2A levels were upregulated in human NSCLC. FAM83A inhibition decreased NSCLC cell growth, motility, and invasiveness, while inducing ferroptosis and enhancing DDP sensitivity. Mechanistically, TFAP2A regulated FAM83A transcription in NSCLC cells. TFAP2A depletion suppressed the malignant behaviors of NSCLC cells and augmented their sensitivity to ferroptosis and DDP, and these effects were reversed by the upregulation of FAM83A. Additionally, TFAP2A depletion decreased the growth of A549 subcutaneous xenografts in vivo. Moreover, the TFAP2A/FAM83A cascade regulated the activation of the PI3K/AKT and Wnt/β-catenin pathways.</p><p><strong>Conclusion: </strong>Our study demonstrates that the novel TFAP2A/FAM83A cascade modulates ferroptosis and drug sensitivity in NSCLC.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"19"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOXD13 knockdown attenuates apoptosis in prostate cancer via the upregulation of MDM2/p53 signaling.","authors":"Yongliang Ma, Pan Qi, Zongtao Ren, Rui Liu, Shufei Wei, Aili Zhang","doi":"10.1186/s13008-025-00161-1","DOIUrl":"10.1186/s13008-025-00161-1","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a common leading cause of death worldwide and is recognized as the second most frequently diagnosed cancer in the male population, making it a significant focus of long-term oncological research. The HOXD13 gene, belonging to the HOX gene family, has been associated with various malignancies, including breast and colon cancer, and is associated with prognostic outcomes. However, its specific role in prostate cancer remains to be elucidated.</p><p><strong>Methods: </strong>The correlation of HOXD13 expression in PCa was analyzed by UALCAN database. qRT-PCR and western blot assays were employed to assess the expression levels of HOXD13 in several prostate cancer cell lines. Construct siRNA and overexpression plasmids for HOXD13 and transfect them into cells. Western blot was used to assess the knockdown efficiency of HOXD13 in the cells. The influence of HOXD13 expression on cell proliferation in PC-3 M and C4-2 cells was assessed by EDU staining. The role of HOXD13 in cell migration and invasion of prostate cancer cells was detected by wound healing and transwell assay. Western blot analysis was performed to examine apoptosis-related proteins (C-caspase3, Bax, and Bcl-2) in PC-3 M cells. The co-immunoprecipitation (Co-IP) assay evaluates the interaction between MDM2 and p53.</p><p><strong>Results: </strong>An examination of the data obtained from the UALCAN database reveals that HOXD13 was significantly reduced in prostate cancer tissues and correlated with patient survival. In prostate cancer cell lines, notably PC-3M, HOXD13 expression was markedly reduced. Knockdown of HOXD13 promotes PC-3 M and C4-2 cells proliferation, migration, and invasion. However, the elevated expression of HOXD13 hampers PC-3 M and C4-2 cells proliferation, migration, and invasion. Furthermore, knockdown of HOXD13 in PC-3 M cells resulted in decreased levels of apoptosis markers, including C-caspase-3 and Bax. Co-immunoprecipitation assays demonstrated that HOXD13 depletion enhanced the association between MDM2 and p53.</p><p><strong>Conclusion: </strong>HOXD13 was a critical regulator in the pathogenesis of prostate cancer, modulating the MDM2/p53 signaling pathway to promote apoptosis.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"18"},"PeriodicalIF":2.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E3 ubiquitin-protein ligase CBL inhibits non-small cell lung cancer progression via ubiquitination and degradation of KDR.","authors":"Zhiyue Tu, Yongshuai Shen, Hua Li","doi":"10.1186/s13008-025-00159-9","DOIUrl":"10.1186/s13008-025-00159-9","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer and continues to be a major cause of cancer-related death globally. The identification of novel molecular targets is essential for developing effective therapeutic strategies.</p><p><strong>Methods: </strong>In this study, we investigated the functional and mechanistic role of the E3 ubiquitin-protein ligase CBL in NSCLC progression. CBL expression was analyzed in NSCLC tumor tissues and cell lines using quantitative RT-PCR and Western blotting. The impact of CBL on NSCLC cell proliferation, migration, and invasion was assessed by a number of in vitro functional tests. Co-immunoprecipitation (Co-IP) and ubiquitination assays were performed to elucidate the molecular interaction between CBL and kinase insert domain receptor (KDR), a key mediator of angiogenesis.</p><p><strong>Results: </strong>CBL expression was markedly reduced in NSCLC tissues and cell lines relative to normal equivalents. Gain- and loss-of-function tests demonstrated that CBL suppressed the NSCLC cell proliferation, migration, and invasion, highlighting its tumor-suppressive role. Mechanistically, CBL regulates KDR protein degradation via ubiquitination, thereby disrupting KDR-mediated signaling pathways associated with angiogenesis and tumor progression. Notably, overexpression of KDR reversed the anti-tumor effects of CBL, restoring the aggressive phenotype of NSCLC cells. These results suggest that CBL acts as a negative regulator of NSCLC malignancy through targeted degradation of KDR.</p><p><strong>Conclusion: </strong>Our findings identify CBL as a functional tumor suppressor in NSCLC that exerts its anti-cancer effects via ubiquitin-mediated degradation of KDR. The CBL-KDR axis signifies a new regulatory route with significant therapeutic potential for NSCLC therapy.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"17"},"PeriodicalIF":2.2,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial fission regulator 2 promotes cell proliferation, migration and invasion in hepatocellular carcinoma through regulating PI3K/AKT signaling pathway.","authors":"Qiang Sun, Kaikun Liu, Fangjie Zheng, Xinwei Chen","doi":"10.1186/s13008-025-00160-2","DOIUrl":"10.1186/s13008-025-00160-2","url":null,"abstract":"<p><strong>Objective: </strong>Mitochondrial fission regulator 2 (MTFR2) is upregulated in multiple cancers, including hepatocellular carcinoma (HCC); however, its mechanistic role in HCC progression remains poorly understood.</p><p><strong>Methods: </strong>MTFR2 expression in HCC tissues was analyzed using TCGA and GEO databases. Validation of MTFR2 expression levels in clinical samples and HCC cell lines was performed through qRT-PCR and western blot. Functional effects of MTFR2 overexpression and knockdown on HCC cell proliferation, migration, and invasion were assessed via CCK-8, colony formation, wound healing, and transwell assays. In vivo tumor growth was evaluated in xenograft mouse models.</p><p><strong>Results: </strong>MTFR2 was significantly overexpressed in HCC tissues and cell lines. Enhanced proliferation, migration, invasion, and colony formation were observed in MTFR2-overexpressing HCC cells, whereas knockdown of MTFR2 suppressed these malignant phenotypes. Mechanistic studies demonstrated that MTFR2 promotes proliferation, migration, and invasion of HCC cells via the PI3K/AKT signaling pathway. Additionally, MTFR2 knockdown significantly attenuated tumor growth in xenograft models.</p><p><strong>Conclusion: </strong>These findings demonstrate that MTFR2 promotes HCC progression via modulation of the PI3K/AKT pathway, underscoring its potential as a therapeutic target for HCC.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"16"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in pancreatic cancer histopathology and diagnostics - implications for clinical decisions and biomarker discovery?","authors":"Petra Weselá, Michal Eid, Petr Moravčík, Jakub Vlažný, Jan Hlavsa, Vladimír Procházka, Zdeněk Kala, Petr Vaňhara","doi":"10.1186/s13008-025-00158-w","DOIUrl":"10.1186/s13008-025-00158-w","url":null,"abstract":"<p><p>Artificial intelligence (AI) and machine learning (ML) are rapidly advancing fields within computer science, driving significant progress in cancer diagnostics. Various ML models have been developed to assist diagnosis, guide therapy decisions, and facilitate early disease detection. In this review, we discuss diverse AI and ML approaches and critically evaluate their applications and limitations in pancreatic cancer histopathology, diagnostics, and biomarker discovery.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"15"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells.","authors":"Yan Liu, Fangle Gu, Jun Gao, Yingyan Gu, Zhiyue Li, Dan Lu, Yanxin Zhang","doi":"10.1186/s13008-025-00154-0","DOIUrl":"10.1186/s13008-025-00154-0","url":null,"abstract":"","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"14"},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UXT enhances melanoma proliferation, migration, and invasion through modulation of the P53 signaling pathway.","authors":"Kaifen Xiong, Chong Wang, Bingqian Hu, Jianglin Zhang, Min Qi","doi":"10.1186/s13008-025-00151-3","DOIUrl":"10.1186/s13008-025-00151-3","url":null,"abstract":"<p><p>Melanoma is a highly malignant skin cancer with significant morbidity and mortality, and current treatments have shown limited efficacy in substantially improving clinical outcomes. This highlights an urgent need for alternative therapeutic strategies. Identifying key factors that promote or inhibit melanoma progression presents a promising approach for developing novel therapeutic targets. The UXT protein levels are increased in multiple human tumor tissues, such as bladder, breast, ovarian, and thyroid cancers, while showing no alteration in the corresponding normal tissues. UXT has previously been shown to be associated with the inhibition of P53, a tumor suppressor factor that plays a crucial role in regulating cancer progression. However, the specific role of UXT in melanoma remains unclear. This study investigates the impact of UXT on melanoma progression, focusing on its effects on cell proliferation, apoptosis, and invasion, alongside its underlying molecular mechanisms. We employed Western blotting, quantitative RT-PCR, immunohistochemistry, CCK-8 assays, colony formation, flow cytometry, wound healing, and invasion assays to explore these functions. Results indicate that UXT is aberrantly upregulated in melanoma cell lines. In vitro experiments demonstrated that silencing UXT inhibited melanoma cell proliferation, migration, and invasion, while also inducing apoptosis. Conversely, overexpression of UXT promoted melanoma cell proliferation, migration, invasion, and facilitated cell cycle progression. In vivo experiments yielded consistent results, showing that UXT knockdown suppressed tumor growth, while UXT overexpression promoted tumor development. Additionally, our study revealed that UXT knockdown activated the p53 signaling pathway in melanoma cells, suggesting that UXT could serve as a potential therapeutic target for melanoma.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"13"},"PeriodicalIF":2.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}