Cancer Biology & Therapy最新文献

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Exosomal miR-122-5p for regulation of secretory functions of fibroblasts and promotion of breast cancer metastasis by targeting MKP-2: an experimental study. 外泌体miR-122-5p通过靶向MKP-2调控成纤维细胞分泌功能并促进乳腺癌转移的实验研究
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-05-04 DOI: 10.1080/15384047.2025.2500104
Yun Lv, Yue Li, Jie Zhou, Xin Liu, Dandan Wang, Dongmei Wang, Dandan Tong, Shuhuai Wang, Hanxiang An, Xinmei Kang
{"title":"Exosomal miR-122-5p for regulation of secretory functions of fibroblasts and promotion of breast cancer metastasis by targeting MKP-2: an experimental study.","authors":"Yun Lv, Yue Li, Jie Zhou, Xin Liu, Dandan Wang, Dongmei Wang, Dandan Tong, Shuhuai Wang, Hanxiang An, Xinmei Kang","doi":"10.1080/15384047.2025.2500104","DOIUrl":"https://doi.org/10.1080/15384047.2025.2500104","url":null,"abstract":"<p><p>Tumor metastasis is a major obstacle for the effective treatment of breast cancer. Some studies showed that exosomes could promote tumor distant metastasis by establishing pre-metastasis niches (PMN). MicroRNAs (miRNAs) in exosomes play a critical role in tumor development and invasion. We aimed to investigate the effects of exosomal miRNAs derived from breast cancer cells on metastasis. MiRNA sequencing and RT-PCR approach were used to screen potential exosomal miRNAs. We compared the levels of serum exosomal miRNAs from breast cancer patients and those from MCF10A/MCF7/MDA-MB-231 cells. We found that differential exosomal miRNAs screened from patients with metastasis have higher expression levels in exosomes secreted by MDA-MB-231 cells. Using miRNA mimics or inhibitors, exosomal miR-122-5p was found to enhance the secretion levels of chemokine MCP-1 and SDF-1 from WI-38 lung fibroblast cells. In vitro luciferase assay and western blot confirmed the targeting of 3'-untranslated region of MKP-2 and suppression of MKP-2 expression by miR-122-5p in WI-38 cells. Treatment of xenograft mice with exosomal miR-122-5p increased the levels of MCP-1 and SDF-1 in serum, and promoted lung metastasis of breast cancer. In conclusion, we identified exosomal miR-122-5p from breast cancer cells that could promote the chemokine secretion of lung fibroblasts, which might facilitate the chemotaxis and colonization of breast cancer cells in lung tissue.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2500104"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MGAT4EP promotes tumor progression and serves as a prognostic marker for breast cancer. MGAT4EP 可促进肿瘤进展,是乳腺癌的预后标志物。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-03-11 DOI: 10.1080/15384047.2025.2475604
Lin Zhong, Jianfeng Zhu, Jie Chen, Xuchu Jin, Liangquan Liu, Shufeng Ji, Jing Luo, Hong Wang
{"title":"MGAT4EP promotes tumor progression and serves as a prognostic marker for breast cancer.","authors":"Lin Zhong, Jianfeng Zhu, Jie Chen, Xuchu Jin, Liangquan Liu, Shufeng Ji, Jing Luo, Hong Wang","doi":"10.1080/15384047.2025.2475604","DOIUrl":"10.1080/15384047.2025.2475604","url":null,"abstract":"<p><p>Breast cancer remains a global health challenge with varied prognoses despite treatment advancements. Therefore, this study explores the pseudogene MGAT4EP as a potential biomarker and therapeutic target in breast cancer. Using TCGA data and bioinformatics, MGAT4EP was identified as significantly overexpressed in breast cancer tissues and associated with poor prognosis. Multivariate Cox regression confirmed MGAT4EP as important prognostic factor. A clinical prediction model based on MGAT4EP expression showed high accuracy for 1-, 3-, and 5-year survival rates and was translated into a nomogram for clinical application. Functional studies revealed that silencing MGAT4EP <i>via</i> siRNA promoted apoptosis, inhibited migration and invasion in breast cancer cells. RNA-seq, GSEA, and GO analyses linked MGAT4EP to apoptosis and focal adhesion pathways. Notably, knock down of MGAT4EP significantly suppressed tumor growth and metastasis in xenograft and lung metastasis models. Taken together, these findings establish MGAT4EP as an attractive target for metastatic breast cancer and provide a potential a promising therapeutic target for breast cancer treatment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2475604"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of extracellular vesicle ZNF280B derived from lung cancer stem cells on lung cancer progression. 肺癌干细胞来源的细胞外囊泡ZNF280B对肺癌进展的影响
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-17 DOI: 10.1080/15384047.2025.2450849
Qixia Guo, Jiayan Lu, Hui Zhao, Ding Zhou, Hua Liu
{"title":"Effect of extracellular vesicle ZNF280B derived from lung cancer stem cells on lung cancer progression.","authors":"Qixia Guo, Jiayan Lu, Hui Zhao, Ding Zhou, Hua Liu","doi":"10.1080/15384047.2025.2450849","DOIUrl":"10.1080/15384047.2025.2450849","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this research was to investigate the role of extracellular vesicles derived from lung cancer stem cells (lung CSCs-EVs) in lung cancer and to explore their potential mechanisms.</p><p><strong>Methods: </strong>Lung CSCs were first isolated and verified using flow cytometry and RT-qPCR assays. Lung CSCs-EVs were extracted through ultracentrifugation and further characterized using transmission electron microscopy and Western blotting. The interaction between lung CSCs-EVs and lung cancer cells was observed through PKH67 staining. Subsequently, we analyzed the differentially expressed genes in lung CSCs using bioinformatics data analysis and evaluated the prognostic value of ZNF280B in lung cancer with the Kaplan-Meier Plotter. RT-qPCR was utilized to assess the mRNA expression levels of these genes, while Western blotting was used to evaluate the protein expression levels of ZNF280B and P53. Next, CCK-8 and colony formation assays were conducted to assess the effects of lung CSCs-EVs and ZNF280B on cancer cell proliferation, migration (via wound healing assay), and invasion (using transwell assay). Additionally, subcutaneous tumor-bearing experiments in nude mice were performed to evaluate the roles of lung CSCs-EVs in lung cancer progression <i>in vivo</i>.</p><p><strong>Results: </strong>The results indicated that lung CSCs-EVs accelerated the progression of lung cancer. Mechanistically, these lung CSCs-EVs transferred ZNF280B into cancer cells, leading to the inhibition of P53 expression.</p><p><strong>Conclusions: </strong>In summary, the manuscript first describes the molecular mechanism by which lung CSCs-EVs promote pro-cancer functions in lung cancer through the ZNF280B/P53 axis.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2450849"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Suppression of pseudogene MT2P1 transcription induced by E2F7 inhibits hepatocellular carcinoma cell proliferation and facilitates apoptosis via preserving its parental gene. E2F7诱导的伪基因MT2P1转录抑制抑制肝癌细胞增殖,并通过保存其亲本基因促进细胞凋亡。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-05-23 DOI: 10.1080/15384047.2025.2510035
Yiquan Lu, Yifan Zhang, Fengjie Hao, Nan Wang, Yongjun Chen, Junqing Wang
{"title":"Suppression of pseudogene MT2P1 transcription induced by E2F7 inhibits hepatocellular carcinoma cell proliferation and facilitates apoptosis via preserving its parental gene.","authors":"Yiquan Lu, Yifan Zhang, Fengjie Hao, Nan Wang, Yongjun Chen, Junqing Wang","doi":"10.1080/15384047.2025.2510035","DOIUrl":"https://doi.org/10.1080/15384047.2025.2510035","url":null,"abstract":"<p><p>The majority of the pseudogenes are inert in normal transcription. Their transcripts are mostly attributed to non-coding RNAs that play various functions in human tumorigenicity and progression. Distinctively, pseudogene MT2P1 is universally transcribed in hepatocytes and presents a significant decrease in hepatocellular carcinoma (HCC). The effect of MT2P1-RNA on HCC cell proliferation and apoptosis needs investigation. MT2P1-RNA was detected by RT-qPCR assay in HCC tissues and cell lines, combined with the exploration of the public databases. The immunohistochemistry assay was used for testing the expression profile of E2F7 and the parental gene MT2A. The clinicopathological features of the patients were collected and analyzed. Ectopic expression of MT2P1-RNA in HCC cell lines was conducted, and the CCK8 assay and flow cytometry assay were carried out. Chromatin immunoprecipitation assay and Dual-luciferase reporter assay were, respectively, applied to validate the interaction between MT2P1, E2F7, and microRNA-15b-5p. The downregulation of MT2P1-RNA in HCC is negatively correlated with dismal clinicopathological features. MT2P1-RNA significantly suppressed HCC cell proliferation and induced apoptosis. E2F7 depletion sequentially elevated the level of MT2P1-RNA and MT2A, and E2F7 was validated as a suppressive transcription factor of the MT2P1 gene. The direct interactions of either MT2P1/miR-15b-5p or miR-15b-5p/MT2A were, respectively, ascertained, enlightening the ceRNA effect of them. The pseudogene-derived MT2P1-RNA is a suppressor of HCC by exerting the ceRNA effect on preserving MT2A, and its transcription is regulated by the suppressive transcription factor E2F7.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2510035"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia. NVP-2联合奥利司他是治疗急性髓系白血病的一种有前景的治疗策略。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-12 DOI: 10.1080/15384047.2025.2450859
Qing Zhu, Jia Cheng, Yuqing Gao, Zimu Zhang, Jian Pan, Xin Su, Danhong Fei, Linbo Cai, Juanjuan Yu, Yanling Chen, Wanyan Jiao, Di Wu, Xiaolu Li, Peifang Xiao
{"title":"NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia.","authors":"Qing Zhu, Jia Cheng, Yuqing Gao, Zimu Zhang, Jian Pan, Xin Su, Danhong Fei, Linbo Cai, Juanjuan Yu, Yanling Chen, Wanyan Jiao, Di Wu, Xiaolu Li, Peifang Xiao","doi":"10.1080/15384047.2025.2450859","DOIUrl":"10.1080/15384047.2025.2450859","url":null,"abstract":"<p><p>Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration. In this study, we knocked down the CDK9 to investigate its effects on the growth and survival of AML cells. Through RNA-seq analysis, we identified that in U937 cells CDK9 regulates numerous genes involved in proliferation and apoptosis, including mTOR, SREBF1, and Bcl-2. Furthermore, our results demonstrated that both CDK9 and FASN are crucial for the proliferation and survival of Kasumi-1 and U937 cells. Mechanistically, MCL1, c-Myc, and Akt/mTOR/SREBF1 may be critical factors and pathways in the combined therapy of NVP-2 and Orlistat. In summary, our study revealed that CDK9 and FASN are vital for maintaining AML cell survival and proliferation. Treatment with NVP-2 and Orlistat may be a promising clinical candidate for patients with AML.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2450859"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PCK2 promotes invasion and epithelial-to-mesenchymal transition in triple-negative breast cancer by promoting TGF-β/SMAD3 signaling through inhibiting TRIM67-mediated SMAD3 ubiquitination. PCK2通过抑制trim67介导的SMAD3泛素化,促进TGF-β/SMAD3信号传导,从而促进三阴性乳腺癌的侵袭和上皮-间质转化。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-03-13 DOI: 10.1080/15384047.2025.2478670
Tsung-Ming Chang, Wei-Yu Fang, Hui-Ping Hsu, Pei-Yi Chu, Shih Sheng Jiang, Kuo-Wei Huang, Wen-Chun Hung, Hui-You Lin, Hui-Jen Tsai
{"title":"<i>PCK2</i> promotes invasion and epithelial-to-mesenchymal transition in triple-negative breast cancer by promoting TGF-β/SMAD3 signaling through inhibiting TRIM67-mediated SMAD3 ubiquitination.","authors":"Tsung-Ming Chang, Wei-Yu Fang, Hui-Ping Hsu, Pei-Yi Chu, Shih Sheng Jiang, Kuo-Wei Huang, Wen-Chun Hung, Hui-You Lin, Hui-Jen Tsai","doi":"10.1080/15384047.2025.2478670","DOIUrl":"10.1080/15384047.2025.2478670","url":null,"abstract":"<p><p><i>PCK2</i>, which encodes mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), is upregulated in various cancers. We demonstrated high expression of PEPCK-M in approximately half of triple-negative breast cancers (TNBCs) previously. TNBC is associated with an aggressive phenotype and a high metastasis rate. In this study, we investigated the role of <i>PCK2</i> in TNBC. <i>PCK2</i> knockdown suppressed proliferation and mTOR signaling in TNBC cells. In addition, cell invasion/migration ability and the expression of epithelial-to-mesenchymal transition (EMT) markers were positively correlated with <i>PCK2</i> expression in TNBC cells via regulation of transforming growth factor-β (TGF-β)/SMAD3 signaling. <i>SMAD3</i> was positively regulated by <i>PCK2</i> in TNBC cells. Knockdown of <i>SMAD3</i> in <i>PCK2</i>-overexpressing TNBC cells reduced the expression levels of EMT markers, Snail and Slug, and suppressed cell invasion/migration. In addition, <i>PCK2</i> knockdown attenuated the stimulatory effect of TGF-β on SMAD3 phosphorylation in TNBC cells. PEPCK-M promotes the protein and mRNA expression of SMAD3 via competitive binding to tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, to reduce SMAD3 ubiquitination, which leads to promoting nuclear translocation of SMAD3 and autoregulation of SMAD3 transcription. Moreover, high <i>PCK2</i> mRNA expression was significantly associated with poor survival in TNBC patients. In conclusion, our study revealed for the first time that <i>PCK2</i> activates TGF-β/SMAD3 signaling by regulating the expression and phosphorylation of SMAD3 by inhibiting TRIM67-mediated SMAD3 ubiquitination and promoting the stimulatory effect of TGF-β to promote TNBC invasion. The regulatory effect of <i>PCK2</i> on mTOR and TGF-β/SMAD3 signaling suggests that <i>PCK2</i> is a potential therapeutic target for suppressing TNBC progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2478670"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A pan-cancer analysis of MARCH8: molecular characteristics, clinical relevance, and immuno-oncology features. MARCH8的泛癌分析:分子特征、临床相关性和免疫肿瘤学特征。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-29 DOI: 10.1080/15384047.2025.2458773
Zihan Quan, Songqing Fan, Hongmei Zheng, Yue Ning, Yang Yang
{"title":"A pan-cancer analysis of MARCH8: molecular characteristics, clinical relevance, and immuno-oncology features.","authors":"Zihan Quan, Songqing Fan, Hongmei Zheng, Yue Ning, Yang Yang","doi":"10.1080/15384047.2025.2458773","DOIUrl":"10.1080/15384047.2025.2458773","url":null,"abstract":"<p><p>Membrane-associated RING-CH8 (MARCH8) is a member of the recently discovered MARCH family of ubiquitin ligases. MARCH8 has been shown to participate in immune responses. However, the role of MARCH8 in prognosis and immunology in human cancers remains largely unknown. The expression of MARCH8 protein was detected via immunohistochemistry in non-small cell lung cancer (NSCLC) and non-cancerous lung tissues. The study investigated the role of MARCH8 in tumor immunity through pan-cancer analysis of multiple databases. MARCH8 genetic alternations and expression were explored with the cBioPortal, GTEx, and TCGA databases. We investigated the role of MARCH8 expression in clinical relevance, prognosis, tumor immune microenvironment, immune checkpoint (ICP) with a series of bioinformatics tools and methods, such as TISIDB database, ESTIMATE, and CIBERSORT method. MARCH8 expression showed cancer-specific dysregulation and was associated with the prognosis of patients in various cancers. MARCH8 was related to the tumor microenvironment and participated in tumor immune regulation. Furthermore, low expression of MARCH8 was associated with poor prognosis and might serve as an independent prognostic biomarker for NSCLC patients. The comprehensive pan-cancer analysis revealed the potential of MARCH8 in tumor-targeted therapy, and suggested MARCH8 as a promising prognostic and immunological pan-cancer biomarker.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2458773"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP. 硫酸酯酶2抑制通过增加细胞外ATP使三阴性乳腺癌细胞对紫杉醇增敏。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-03-26 DOI: 10.1080/15384047.2025.2483989
Jasmine M Manouchehri, Jharna Datta, Lynn M Marcho, Daniel Stover, Ramesh K Ganju, Bhuvaneswari Ramaswamy, William E Carson, Arjun Mittra, Xiaoli Zhang, Patrick M Schnell, Yu Yue, Mark P Rubinstein, Mathew A Cherian
{"title":"Sulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP.","authors":"Jasmine M Manouchehri, Jharna Datta, Lynn M Marcho, Daniel Stover, Ramesh K Ganju, Bhuvaneswari Ramaswamy, William E Carson, Arjun Mittra, Xiaoli Zhang, Patrick M Schnell, Yu Yue, Mark P Rubinstein, Mathew A Cherian","doi":"10.1080/15384047.2025.2483989","DOIUrl":"10.1080/15384047.2025.2483989","url":null,"abstract":"<p><p>The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functional group essential for ATPase inhibition. Consequently, we propose that TNBC cell death and eATP release induced by chemotherapy would be intensified by SULF2 inhibitors. We examined eATP and cell viability in paclitaxel-treated TNBC and nontumorigenic immortal mammary epithelial MCF-10A cells in the presence of OKN-007, a selective SULF2 inhibitor, and/or heparan sodium sulfate. Furthermore, sulfatase 1 (SULF1) and SULF2 protein expressions were ascertained. We found that the expression of SULF2 was greater in TNBC cell lines when compared to MCF-10A cells. The release of eATP and loss of TNBC cell viability induced by chemotherapy was enhanced by OKN-007. The co-treatment of chemotherapy and OKN-007 also attenuated cancer-initiating cells. This data implies that the combination of SULF2 inhibitors with chemotherapy augments eATP and decreases cell viability of TNBC greater than chemotherapy alone.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2483989"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights into the molecular and genetic role of obesity in breast cancer pathogenesis. 肥胖症在乳腺癌发病机制中的分子和遗传作用。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-05-12 DOI: 10.1080/15384047.2025.2501345
Sandeep Mallya, Varsha Gangadhar, Sophia Evangeline Aldrin, Meghana Acharya, Shama Prasada Kabekkodu, Kiran Kumar Kolathur, Sanjiban Chakrabarty
{"title":"Insights into the molecular and genetic role of obesity in breast cancer pathogenesis.","authors":"Sandeep Mallya, Varsha Gangadhar, Sophia Evangeline Aldrin, Meghana Acharya, Shama Prasada Kabekkodu, Kiran Kumar Kolathur, Sanjiban Chakrabarty","doi":"10.1080/15384047.2025.2501345","DOIUrl":"10.1080/15384047.2025.2501345","url":null,"abstract":"<p><p>The epidemic of obesity is a growing concern and is one of the major risk factors for several chronic diseases, including several types of cancers. The correlation of breast cancer with obesity has been extensively studied and involves an interplay of hormonal, metabolic, and genetic factors explored in this review. Inflammation and hormone dysregulation play an important role in promoting a protumorigenic environment through adipose tissue, which is involved in energy storage and functions as an endocrine organ. As a result, various cytokines, primarily proinflammatory in nature, are released, resulting in low-grade inflammation promoting tumor growth. Additionally, obese conditions also induce imbalances in hormones, particularly estrogen and insulin, both of which drive carcinogenesis. Genetic components such as single nucleotide polymorphisms also play critical roles in modulating the correlation between obesity and breast cancer. This review provides a comprehensive overview of various mechanisms underlying obesity and breast cancer incidence and progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2501345"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Silencing ZIC5 suppresses glycolysis and promotes disulfidptosis in lung adenocarcinoma cells. 沉默ZIC5抑制糖酵解并促进肺腺癌细胞的二亢。
IF 4.4 4区 医学
Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-05-14 DOI: 10.1080/15384047.2025.2501780
Cimei Zeng, Denggao Huang, Lei Wang, Haimei Liang, Ximiao Ma
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