Cellular Oncology最新文献

{"title":"The ubiquitin-like protein FAT10 enhances the autophagy-mediated degradation of ZO-1 by stabilizing ATG3 to promote the lung metastasis of colon cancer.","authors":"Zijing Li, Hengqing Zhu, Dongnian Du, Dandan Zhang, Xuzhe Yu, Fei Xie, Miao Ye, Qing Wang, Rong Wan, Jin Ge, Jianghua Shao","doi":"10.1007/s13402-026-01220-7","DOIUrl":"https://doi.org/10.1007/s13402-026-01220-7","url":null,"abstract":"<p><strong>Purpose: </strong>The ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) directs substrates to the 26 S proteasome, but its role in autophagic protein degradation remains unclear.</p><p><strong>Methods: </strong>FAT10 expression was analyzed by qRT-PCR and western blotting in colon cancer (CC) tissues and cells. Bioinformatics revealed FAT10-associated biological processes in CC. In vitro and in vivo assays examined CC cell invasion and metastasis. Autophagy was assessed by western blotting, mRFP-GFP-LC3 reporter (tfLC3), and electron microscopy. In vitro ubiquitination assays measured ubiquitination of zona occludens 1 (ZO-1) and autophagy-related gene 3 (ATG3). liquid chromatography‒tandem mass spectrometry (LC-MS/MS) identified FAT10-interacting proteins. Co-IP and GST pull-down confirmed FAT10-ATG3 binding.</p><p><strong>Results: </strong>FAT10 was upregulated in CC tissues and cells. Bioinformatic analyses revealed that FAT10 expression was correlated with extracellular matrix binding and cell migration in CC. FAT10 overexpression enhanced CC invasion and metastasis. FAT10 promoted autophagic degradation of ZO-1, a key component of tight junctions, facilitating invasion and migration. Mechanistically, FAT10 stabilized ATG3 by competing with ubiquitin for binding, inhibiting ATG3 ubiquitination and activating autophagy, leading to ZO-1 degradation. The ATG3 inhibitor compound 189 reversed FAT10-induced ZO-1 loss and suppressed lung metastasis.</p><p><strong>Conclusion: </strong>Our findings demonstrate a novel pathway by which FAT10 activates autophagy by stabilizing ATG3, leading to ZO-1 degradation and promoting CC lung metastasis. This study provides new insights into the role of FAT10 in regulating protein homeostasis and offers a potential strategy for targeting the FAT10-ATG3-autophagy axis in the treatment of CC metastasis.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845060","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":"Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis.","authors":"Jie Ding, Jingbing Pan, Wenduo Xue, Siyuan Ying, Siyu Zuo, Runhe Xia, Yandong Li, Ming Quan","doi":"10.1007/s13402-026-01205-6","DOIUrl":"https://doi.org/10.1007/s13402-026-01205-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by profound chemoresistance, creating an urgent need for novel therapies to overcome treatment failure. Although stiripentol has shown antitumour activity in glioblastoma (GBM), its precise mechanism of action remains unclear. Further investigation is needed to elucidate both its therapeutic efficacy and the underlying molecular mechanisms in PDAC.</p><p><strong>Methods: </strong>This study validated the proposed mechanisms and therapeutic efficacy through a multi-faceted approach integrating transcriptomic and metabolomic analyses, complemented by both in vivo and in vitro experiments.</p><p><strong>Results: </strong>CCK8, EdU, and colony formation assays demonstrated that stiripentol inhibited the proliferation of PDAC cells in vitro. PI staining and Western blotting (WB) confirmed that stiripentol induced pyroptosis in PDAC cells cultured under low-serum (1% FBS) condition. Integrated multiomics (RNA-seq and lipid metabolomics), combined with functional validation, revealed that stiripentol triggered endoplasmic reticulum (ER) stress and pyroptosis via SREBP1-SCD/FADS2 pathway-mediated disruption of saturated/unsaturated fatty acids (SFAs/UFAs) homeostasis. Finally, we confirmed that stiripentol synergized with gemcitabine (GEM) to suppress PDAC growth both in vitro and in vivo.</p><p><strong>Conclusions: </strong>Our findings demonstrate that stiripentol disrupts SFAs/UFAs homeostasis, thereby inducing ER stress and pyroptosis in PDAC cells under serum deprivation condition. Notably, stiripentol has synergistic antitumour effects with GEM, highlighting its translational potential as a promising combination therapy for PDAC treatment.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845131","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":"Pharmacological inhibition of PGK1 suppresses EGFR-positive esophageal squamous cell carcinoma by dual targeting of glycolysis and autophagy-dependent EGFR degradation.","authors":"Juan Ge, Yongfei Chen, Zongru Jiang, Shuang Qi, Jie Hu, Beilei Wang, Aoli Wang, Qingsong Liu, Hong Wu, Wenchao Wang, Jing Liu","doi":"10.1007/s13402-026-01215-4","DOIUrl":"10.1007/s13402-026-01215-4","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787168","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":"EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.","authors":"Lan Li, YiRan Yang, Dan Li, ChuMao Chen, XinMei Mu, JiaXin Wu, Jin Yuan","doi":"10.1007/s13402-026-01212-7","DOIUrl":"https://doi.org/10.1007/s13402-026-01212-7","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MIF-CD74 axis drives colorectal cancer via glycolytic reprogramming and is targeted by a novel small-molecule inhibitor.","authors":"Jinwei Lou, Yuhan Chen, Yue Li, Zixuan Liu, Shangshang Hu, Muzi Ding, Jian Qin, Huiling Sun, Yuqin Pan","doi":"10.1007/s13402-026-01202-9","DOIUrl":"https://doi.org/10.1007/s13402-026-01202-9","url":null,"abstract":"<p><strong>Background: </strong>Macrophage migration inhibitory factor (MIF) promotes inflammation, regulates immune responses and chemotherapy resistance in the tumor microenvironment. However, its mechanism of action in colorectal cancer (CRC) metabolic reprogramming and targeted therapeutic potential remain unclear. This study aims to investigate the function, mechanism, and targeted therapeutic potential of MIF in CRC.</p><p><strong>Methods: </strong>Data were integrated from TCGA, GTEx, CPTAC, and HPA databases with clinical sample validation. Single-cell sequencing analysis (datasets GSE166555 and GSE144735) was performed, alongside functional assays and mechanistic studies. A novel high-potency MIF inhibitor was identified through virtual screening and validated in vitro and in vivo.</p><p><strong>Results: </strong>MIF expression was found to be significantly elevated in CRC tissues and cell lines, correlating with poor overall survival (OS) and disease-specific survival (DSS). Single-cell sequencing confirmed malignant epithelial cells as the primary MIF source. Functional assays demonstrated that MIF knockout suppressed CRC cell proliferation, migration, and tumor growth in vivo, while MIF overexpression promoted these effects. Mechanistically, MIF binds CD74 to upregulate glycolytic enzymes (HK2, PKM2, LDHA), enhancing glucose uptake and lactate/pyruvate production, thereby driving the Warburg effect and CRC progression. Virtual screening identified a novel high-potency MIF inhibitor, F3277-0933 (IC50 = 8.284 μM). In vitro and in vivo, F3277-0933 surpassed the classical inhibitor ISO-1 in suppressing MIF-driven glycolytic reprogramming and proliferation.</p><p><strong>Conclusion: </strong>This study elucidates a novel mechanism by which the MIF-CD74 axis drives CRC progression through glycolytic reprogramming and provides robust preclinical evidence for developing MIF-targeted therapies.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787225","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":"ASCL2 drives colorectal cancer metastasis through transcriptional activation of TDGF1.","authors":"Defu Li, Hui Wang, Zhengping Yu, Yuanbing Zhang, Jie Zhang, Xiang Tao, Fangping Wang, Shiwen Luo, Quqin Lu","doi":"10.1007/s13402-026-01213-6","DOIUrl":"10.1007/s13402-026-01213-6","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730749","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":"Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.","authors":"Xiaodong Wang, Di Xiong, Songli Cui, Bingchen Duan, Gouping Ding, Yiping Huang, Qianqian Wang","doi":"10.1007/s13402-026-01186-6","DOIUrl":"10.1007/s13402-026-01186-6","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730727","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":"Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.","authors":"Hong Jiang, Kan Li, Yahui Wang, Qiuhan Zheng, Huanzi Lu, Dikan Wang, Jianghai Chen, Guiqing Liao, Yujie Liang","doi":"10.1007/s13402-026-01198-2","DOIUrl":"10.1007/s13402-026-01198-2","url":null,"abstract":"<p><strong>Background: </strong>Surgery is the first choice of treatment for oral squamous cell carcinoma (OSCC), including primary tumor resection and neck dissection. However, neck dissection of early-stage OSCC patients is still controversial. Exploration of mechanisms of early-stage OSCC metastasis might help to guide treatment choice. Our previous research has demonstrated that matrix stiffness activated the PERK-associated unfolded protein response (UPR), thereby contributing to early-stage OSCC metastasis. Since stress granules (SGs) are also regulated by PERK-mediated UPR, our study aimed to identify stiffness-related SGs and decipher their function of modulating early-stage OSCC metastasis.</p><p><strong>Methods: </strong>At first, we evaluated matrix stiffness and SGs level in early-stage OSCC tissues. Then enhanced matrix stiffness was simulated in vivo and its effect on metastasis and SGs expression was observed. Furthermore, A force loading model was adopted to identify the stiffness-related SGs in vitro and the effects of stiffness-related SGs on metastasis were further evaluated in vitro and in vivo. We identified the unique type of SGs which was stiffness-related to adopt mechanical stimuli. The stiffness-related SGs may boost metastasis cascade through promotion of anoikis resistance. At last, we investigated the containing mRNAs of stiffness-related SGs through RNA Immunoprecipitation Sequencing.</p><p><strong>Results: </strong>The stiffness-related SGs were identified which may boost metastasis cascade through promotion of anoikis resistance. The unique SGs were rich in mRNA related to negative regulation of apoptosis, partly explained the anoikis resistance associated with stiffness-related SGs.</p><p><strong>Conclusions: </strong>The stiffness-related SGs may protect the disseminated cancer cells from anoikis resistance by harboring the set of specific mRNAs. Matrix stiffness promotes the formation of SGs in OSCC, getting prepared for metastasis in the early stage.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730744","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":"CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.","authors":"Xuchu Jin, Yu Liu, Xinyu Zheng, Yangke He","doi":"10.1007/s13402-026-01211-8","DOIUrl":"10.1007/s13402-026-01211-8","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730664","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":"Liquid biopsy in the clinical management of tumor of urinary system: current status and future developments.","authors":"Runsen Xu, Yiming Zhao, Peng Su, Lin Li, Hongyuan Liang, Dan Dong, Kefeng Wang","doi":"10.1007/s13402-026-01216-3","DOIUrl":"10.1007/s13402-026-01216-3","url":null,"abstract":"","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":"49 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730730","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}