Cellular Oncology最新文献

{"title":"Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.","authors":"Haksoo Lee, Sujin Park, Jongwon Lee, Chaeyoung Lee, Hyunkoo Kang, JiHoon Kang, Jung Sub Lee, Eunguk Shin, HyeSook Youn, BuHyun Youn","doi":"10.1007/s13402-025-01081-6","DOIUrl":"https://doi.org/10.1007/s13402-025-01081-6","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a highly plastic subpopulation of tumor cells with capabilities for self-renewal, therapy resistance, and metastasis. Recent evidence highlights lipid metabolic reprogramming as a central mechanism supporting these malignant traits. This review synthesizes current findings on key lipid metabolic processes in CSCs-including lipid uptake via CD36, intracellular storage in lipid droplets, de novo fatty acid synthesis by fatty acid synthase (FASN), fatty acid oxidation (FAO) regulated by carnitine palmitoyltransferase 1A (CPT1A), and cholesterol biosynthesis through the mevalonate pathway. Although many of these pathways are active in bulk cancer cells, CSCs demonstrate greater functional reliance on them, leading to enhanced survival, redox balance, and adaptation to therapy. These metabolic preferences vary by cancer type, underscoring the need for context-specific approaches. Moreover, stromal components of the tumor microenvironment (TME), such as cancer-associated fibroblasts, adipocytes, and mesenchymal stem cells, modulate CSC lipid metabolism through paracrine signals and substrate transfer, reinforcing CSC maintenance and drug resistance. Therapeutic strategies targeting lipid metabolism-such as inhibition of SCD1, CPT1A, and HMG-CoA reductase-have shown promising preclinical results in selectively depleting CSC populations and sensitizing tumors to treatment. However, challenges remain in preserving normal stem cell function, which also depends on lipid pathways. This review underscores the emerging significance of lipid metabolism as both a hallmark and vulnerability of CSCs, offering opportunities for novel targeted cancer therapies.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530709","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":"Trends in immunotherapy for oral squamous cell carcinoma.","authors":"Ningning Xue, Ying Wang, Ziyuan Wang, Xin Zeng, Jiongke Wang, Xuefeng Zhang","doi":"10.1007/s13402-025-01068-3","DOIUrl":"https://doi.org/10.1007/s13402-025-01068-3","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor of the head and neck, characterized by an immunosuppressive tumor microenvironment. The traditional treatment approach for OSCC typically involves a combination of surgical resection, radiotherapy, and chemotherapy. Over the last few decades, the 5-year overall survival rate for OSCC has remained relatively stagnant at approximately 50-60%. Recently, the rapid progress in immunotherapy has revolutionized OSCC treatment, particularly through the use of immune checkpoint blockade therapies. Nivolumab and pembrolizumab have been approved by the US Food and Drug Administration (FDA) for the immunotherapy of head and neck squamous cell carcinoma (HNSCC). Additionally, other modalities such as costimulatory agonists, adoptive cellular therapy, cytokine immunotherapy, cancer vaccines, and photoimmunotherapy have shown promising feasibility and efficacy in relevant preclinical and clinical studies. Future directions for OSCC immunotherapy include precision medicine and research into the pathogenesis of immune-related adverse events (irAEs) and standardization of management methods. Furthermore, nano-immunotherapy is expected to be a significant trend in OSCC treatment. Clinical trial number Not applicable.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477495","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":"Synthetic NKG2D receptor (SNR) armored CAR-T cells overcome antigen heterogeneity of solid tumor.","authors":"Minmin Sun, Linke Bian, Hongye Wang, Xin Liu, Yantao Li, Zhaorong Wu, Shuangshuang Zhang, Ruidong Hao, Hong Xin, Bo Zhai, Xuemei Zhang, Yuanguo Cheng","doi":"10.1007/s13402-025-01066-5","DOIUrl":"https://doi.org/10.1007/s13402-025-01066-5","url":null,"abstract":"<p><strong>Background: </strong>CAR-T cell therapy has demonstrated remarkable success in hematologic malignancies; however, its effectiveness against solid tumors remains limited due to tumor antigen heterogeneity. NKG2DLs, including MICA/B and the ULBP family, are stress-induced molecules frequently upregulated on the surface of tumor cells and components of the tumor microenvironment, providing attractive targets for immunotherapy. To broaden the targeting capability beyond conventional Claudin18.2-directed CAR-T cells, we engineered a Synthetic NKG2D Receptor (SNR). The SNR comprises the extracellular domain of NKG2D fused with the intracellular signaling domains of DAP10 and DAP12, enabling effective targeting of NKG2D ligands (NKG2DLs).</p><p><strong>Methods: </strong>Expression of NKG2DLs and CLDN18.2 were detected by immunohistochemistry on a gastric cancer tissue microarray. We designed SNR CAR-T cells by linking CLDN18.2 CAR with SNR by a 2A self-cleaving peptide. We assessed their cytotoxicity, tumor infiltration, persistence, and antitumor efficacy using in vitro assays, patient-derived xenograft (PDX) models, and murine syngeneic models. Additionally, transcriptomic analysis and flow cytometry were performed to evaluate exhaustion and memory markers.</p><p><strong>Results: </strong>SNR CAR-T cells demonstrated enhanced cytotoxicity against tumor cells with heterogeneous CLDN18.2 expression, effectively lysing both CLDN18.2-positive and NKG2DL-positive tumor cells in vitro. In PDX and murine models, SNR CAR-T cells exhibited superior antitumor efficacy, leading to significant tumor regression and CAR-T expansion compared to conventional CAR-T cells. Furthermore, SNR CAR-T cells displayed reduced expression of exhaustion markers and increased expression of memory-associated markers. Enhanced tumor infiltration, proliferation and cytotoxicity within the tumor microenvironment, and a reduced presence of myeloid-derived suppressor cells (MDSCs) and tumor neovasculature were observed. Importantly, SNR CAR-T cell therapy was well-tolerated, with no significant toxicity noted in all the treated animals.</p><p><strong>Conclusion: </strong>The SNR CAR-T cell approach addresses tumor antigen heterogeneity and suppressive tumor microenvironment, offering a promising therapeutic strategy for solid tumors and paving the way for its future clinical applications.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327502","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":"Absence of lipopolysccharide (LPS) expression in breast cancer cells.","authors":"Noel F C C de Miranda, Vincent T H B M Smit, Manon van der Ploeg, Jelle Wesseling, Jacques Neefjes","doi":"10.1007/s13402-025-01071-8","DOIUrl":"https://doi.org/10.1007/s13402-025-01071-8","url":null,"abstract":"<p><p>The relationship between bacterial activity and tumorigenesis has gained attention in recent years, complementing the well-established association between viruses and cancer. A recent study employed immunodetection of lipopolysaccharide (LPS) to demonstrate the presence of intracellular bacteria within cancer cells across various cancer types, including breast cancer. The authors proposed that these bacteria might play a role in tumor development. We sought to replicate these findings using the same experimental methods on an independent cohort of breast cancer cases. Our analysis of 129 samples revealed no evidence of LPS expression within cancer cells. Instead, LPS immunoreactivity was observed in ducts or immune cells, specifically macrophages, as expected. These discrepancies in LPS immunodetection warrant caution in interpreting the original findings, and further research is needed to clarify the potential role of intracellular bacteria in cancer development.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267789","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":"SPTSSA facilitates gastric cancer progression with modulating PD-L1 in immunomicroenvironment through Wnt/β-catenin pathway.","authors":"Pingping Sun, Weiwei Qin, Haiyan Xu, Hang Yin, Lei Yang, Xiaojing Zhang, Xiaoxia Jin, Qiang Xu, Han Wu, Xiaoling Kuai, Lizhou Jia, Jianfei Huang, Yao Wang","doi":"10.1007/s13402-025-01072-7","DOIUrl":"https://doi.org/10.1007/s13402-025-01072-7","url":null,"abstract":"<p><strong>Purpose: </strong>Gastric cancer (GC) remains a considerable global health concern, underscoring the necessity for dependable biomarkers for its diagnosis and treatment. This investigation seeks to investigate the clinical predictive value and functional roles of SPTSSA in GC.</p><p><strong>Methods: </strong>The mRNA expression of SPT family molecules was analyzed through bioinformatics approaches. In vitro and in vivo studies assessed the function of SPTSSA in the malignant progression of GC. Additionally, SPTSSA protein levels in GC tissues and peripheral venous blood were measured using immunofluorescence staining and enzyme-linked immunosorbent assay, respectively. The link between SPTSSA expression and immune cell infiltration in GC was also evaluated by multiplex immunohistochemistry.</p><p><strong>Results: </strong>Patients exhibiting elevated levels of SPTSSA mRNA experienced the poorest prognosis in comparison to other members of the SPT family. SPTSSA overexpression enhanced the malignant phenotype of GC in in vitro and in vivo experiments. Mechanistically, SPTSSA facilitated the accumulation of β-catenin and the transcription of programmed death ligand 1 (PD-L1) through the Wnt signaling pathway. SPTSSA protein levels were markedly elevated in both GC tissues and peripheral venous blood. Furthermore, increased expression of SPTSSA was linked to a reduction in CD8⁺ T cell infiltration, heightened M2 macrophage infiltration, and increased PD-L1 expression in GC patients.</p><p><strong>Conclusion: </strong>SPTSSA promotes GC progression by modulating PD-L1 expression in immunomicroenvironment via the Wnt signaling pathway. Consequently, SPTSSA emerges as a promising new prognostic indicator and a potential therapeutic target for GC management.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267791","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":"GMPS inhibits the proliferation and migration of non-small cell lung cancer via the regulation of the DNMT 1/SERPINB2 axis.","authors":"Tingting Guo, Lei Liu, Lingyan Zeng, Ying Yang, Tingting Song, Huachang Zhao, Zhixin Qiu","doi":"10.1007/s13402-025-01078-1","DOIUrl":"https://doi.org/10.1007/s13402-025-01078-1","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) mainly includes lung squamous cell carcinoma and lung adenocarcinoma, and its extremely high morbidity and mortality are the main causes of poor prognosis in NSCLC patients. Therefore, it is particularly important to study the mechanisms associated with tumor proliferation and metastasis and explore new molecular targets of NSCLC. Studies have shown that Guanosine monophosphate synthase (GMPS) may serve as a potential drug target, but its biological function and molecular mechanism in NSCLC are still unknown. Therefore, it is urgently needed to investigate the molecular mechanisms of GMPS.</p><p><strong>Methods: </strong>We first analyzed 30 cases of lung adenocarcinoma, lung squamous carcinoma and adjacent tissues; Then, lentiviral technology was used to construct overexpressed or knocked out cell lines to verify the function of GMPS. Then, RNA sequencing and Western blot experiments were carried out in animal experiments to explore the mechanism of GMPS. Our experimental results suggest that GMPS plays an important role in the progression of NSCLC.</p><p><strong>Results: </strong>We found that GMPS was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma tissues, and was associated with poor prognosis of patients. Down-regulation of GMPS inhibits tumor progression. And GMPS promotes lung cancer cell migration through the SERPINB2-uPA axis, and DNMT1 is an intermediate factor in GMPS regulating SERPINB2 expression. Our experimental results show that GMPS expression is associated with lung cancer invasion and migration.</p><p><strong>Conclusions: </strong>Our findings revealed the correlation between GMPS and the prognosis of NSCLC at the tissue level. Secondly, GMPS can promote the progression of NSCLC. The molecular mechanism of GMPS affecting the metastasis of lung cancer cells was elucidated. These findings highlight the important role of GMPS in NSCLC, so as to provide new insights for the identification of new targets and lay a theoretical foundation for the clinical application of GMPS.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267790","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":"High extracellular matrix stiffness upregulates TNNT1 to awaken dormant tumor cells in liver metastatic niches of gastric cancer.","authors":"Linhua Ji, Jie Peng, Yuxuan Lin, Yiqing Zhong, Bo Ni, Chunchao Zhu, Zizhen Zhang","doi":"10.1007/s13402-025-01053-w","DOIUrl":"10.1007/s13402-025-01053-w","url":null,"abstract":"<p><strong>Background: </strong>Liver is one of the target organs bearing the most frequent distant metastasis of gastric cancer (GC), and patients with GC liver metastasis suffering from poor prognosis. According to \"seed and soil\" theory, important and complex interactions between disseminated tumor cells (DTCs) and metastasis tumor microenvironment (MTM) have played a vital role in waking the dormant DTCs and promoting their proliferation. We have discovered that the aberrantly activated cancer associated fibroblasts (CAFs) could significantly increase the enrichment and stiffness of extracellular matrix (ECM). ECM with high stiffness could facilitate the accumulation of Troponin T1, slow skeletal type (TNNT1) in cytoplasm for dormant DTCs awaking and proliferation.</p><p><strong>Methods: </strong>We set off from observing the stiffness of ECM around liver metastatic niches of GC and performed in vivo and in vitro study for further study. Based on the gained information, we plan to further unveil the underlying mechanism and explore the clinical transformation value using the ex-vivo and patient derived xenograft (PDX) model.</p><p><strong>Conclusion: </strong>Our study aims to illustrate the relationship between ECM stiffness and tumor dormancy awakening in liver metastasis of GC and provide reliable theoretical and research basis for treatment of GC liver metastasis.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"815-834"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041514","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":"Enhanced ZBTB10 expression induced by betulinic acid inhibits gastric cancer progression by inactivating the ARRDC3/ITGB4/PI3K/AKT pathway.","authors":"Zhixin Huang, Ying Li, Zeyu Zhao, Linying Ye, Tianhao Zhang, Zihan Yu, Ertao Zhai, Yan Qian, Xiang Xu, Risheng Zhao, Shirong Cai, Jianhui Chen","doi":"10.1007/s13402-025-01039-8","DOIUrl":"10.1007/s13402-025-01039-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) ranks as the fourth leading cause of cancer-related deaths worldwide, with most patients diagnosed at advanced stages due to the absence of reliable early detection biomarkers.</p><p><strong>Methods: </strong>RNA-sequencing was conducted to identify the differentially expressed genes between GC tissues and adjacent normal tissues. CCK8, EdU, colony formation, transwell, flow cytometry and xenograft assays were adopted to explore the biological function of ZBTB10 and betulinic acid (BA) in GC progression. RNA-sequencing and phospho-proteomic profiling were performed to analyze the signaling pathways associated with ZBTB10-inhibiting GC progression. Chromatin immunoprecipitation, Co-immunoprecipitation and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of ZBTB10 in GC.</p><p><strong>Results: </strong>ZBTB10 was one of the most significantly downregulated genes in GC tissues, and higher expression levels of ZBTB10 was correlated with better prognosis in patients with GC. Functional studies revealed that ZBTB10 overexpression and BA inhibited GC progression both in vitro and in vivo. Mechanistically, ZBTB10 enhanced ARRDC3 expression by binding to a specific response element in the ARRDC3 promoter region. Elevated ARRDC3 then directly interacted with β-4 integrin (ITGB4), leading to its ubiquitination and degradation. This cascade ultimately resulted in the downregulation of PI3K and AKT phosphorylation level. Moreover, ZBTB10 was a key target for BA in GC and BA inhibited GC progression through regulating the ZBTB10/ARRDC3/ITGB4/PI3K/AKT axis.</p><p><strong>Conclusions: </strong>Our findings reveal that BA holds promise as an effective therapeutic strategy for GC, and the ZBTB10/ARRDC3/ITGB4/PI3K/AKT axis may serve as a novel diagnostic and therapeutic target.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"675-692"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053947","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":"Predicting the early therapeutic response to hepatic artery infusion chemotherapy in patients with unresectable HCC using a contrast-enhanced computed tomography-based habitat radiomics model: a multi-center retrospective study.","authors":"Mingsong Wu, Zenglong Que, Shujie Lai, Guanhui Li, Jie Long, Yuqin He, Shunan Wang, Hao Wu, Nan You, Xiang Lan, Liangzhi Wen","doi":"10.1007/s13402-025-01041-0","DOIUrl":"10.1007/s13402-025-01041-0","url":null,"abstract":"<p><strong>Objective: </strong>Predicting the therapeutic response before initiation of hepatic artery infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) remains challenging for patients with unresectable hepatocellular carcinoma (HCC). Herein, we investigated the potential of a contrast-enhanced CT-based habitat radiomics model as a novel approach for predicting the early therapeutic response to HAIC-FOLFOX in patients with unresectable HCC.</p><p><strong>Methods: </strong>A total of 148 patients with unresectable HCC who received HAIC-FOLFOX combined with targeted therapy or immunotherapy at three tertiary care medical centers were enrolled retrospectively. Tumor habitat features were extracted from subregion radiomics based on CECT at different phases using k-means clustering. Logistic regression was used to construct the model. This CECT-based habitat radiomics model was verified by bootstrapping and compared with a model based on clinical variables. Model performance was evaluated using the area under the curve (AUC) and a calibration curve.</p><p><strong>Results: </strong>Three intratumoral habitats with high, moderate, and low enhancement were identified to construct a habitat radiomics model for therapeutic response prediction. Patients with a greater proportion of high-enhancement intratumoral habitat showed better therapeutic responses. The AUC of the habitat radiomics model was 0.857 (95% CI: 0.798-0.916), and the bootstrap-corrected concordance index was 0.842 (95% CI: 0.785-0.907), resulting in a better predictive value than the clinical variable-based model, which had an AUC of 0.757 (95% CI: 0.679-0.834).</p><p><strong>Conclusion: </strong>The CECT-based habitat radiomics model is an effective, visualized, and noninvasive tool for predicting the early therapeutic response of patients with unresectable HCC to HAIC-FOLFOX treatment and could guide clinical management and decision-making.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"709-723"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191102","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":"Exosomes delivering miR-129-5p combined with sorafenib ameliorate hepatocellular carcinoma progression via the KCTD1/HIF-1α/VEGF pathway.","authors":"Xinyu Zhu, Zhiwei Li, Li Chen, Limin Li, Mi Ouyang, Hao Zhou, Kai Xiao, Ling Lin, Paul K Chu, Chang Zhou, Chengfeng Xun, Liu Yang, Wenhuan Huang, Xiaofeng Ding","doi":"10.1007/s13402-025-01044-x","DOIUrl":"10.1007/s13402-025-01044-x","url":null,"abstract":"<p><strong>Background: </strong>Potassium channel tetramerization domain-containing 1 (KCTD1) plays a critical role in transcriptional regulation and adipogenesis, but its significance in hepatocellular cancer (HCC) has not been reported.</p><p><strong>Methods: </strong>Immunohistochemistry, Western blotting and quantitative real-time PCR analysis were performed to assess the expression of KCTD1 and related genes in HCC cells. MTT assays, colony formation, cell migration, invasion and the in-vivo mouse models were utilized to evaluate the function of KCTD1 in HCC progression. Co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assays were conducted to elucidate the molecular mechanisms of KCTD1 in HCC.</p><p><strong>Results: </strong>KCTD1 expression was increased in human HCC tissues and closely associated with advanced tumor stages. KCTD1 overexpression enhanced growth, migration, and invasion of Huh7 and HepG2 cells both in vitro and in vivo, while KCTD1 knockdown reversed these effects in MHCC97H cells. Mechanistically, KCTD1 interacted with hypoxia-inducible factor 1 alpha (HIF-1α) and enhanced HIF-1α protein stability with the inhibited prolyl-hydroxylases (PHD)/Von Hippel-Lindau (VHL) pathway, consequently activating the Vascular Endothelial Growth Factor (VEGF)/VEGFR2 pathway in HCC cells. Sorafenib and KCTD1 knockdown synergistically inhibited intrahepatic tumor growth following in situ injection of MHCC97H cells. miR-129-5p downregulated KCTD1 by binding to KCTD1 3'UTR. Finally, 45 µg exosomes from miR-129-5p-overexpressing MHCC97H cells combined with 25 mg/kg sorafenib to decrease HCC tumor size.</p><p><strong>Conclusions: </strong>These results suggested that KCTD1 protects HIF-1α from degradation and activates the VEGF signaling cascade to enhance HCC progression. Therefore, KCTD1 may serve as a novel target of HCC and pave the way for an efficient combined therapy in advanced HCC.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"743-760"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993428","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}