Cancer letters最新文献_第10页

Selective removal of proteins and microvesicles ex vivo from blood of pancreatic cancer patients using bioengineered adsorption filters

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-12 DOI: 10.1016/j.canlet.2025.217546

Richard T. Waldron , Ruoxiang Wang , Stephanie N. Shishido , Aurelia Lugea , Ahmed G. Ibrahim , Jeremy Mason , Matthew Ayres , Sarah J. Parker , Jennifer E. Van Eyk , Simon K. Lo , Peter Kuhn , Stephen J. Pandol

{"title":"Selective removal of proteins and microvesicles ex vivo from blood of pancreatic cancer patients using bioengineered adsorption filters","authors":"Richard T. Waldron , Ruoxiang Wang , Stephanie N. Shishido , Aurelia Lugea , Ahmed G. Ibrahim , Jeremy Mason , Matthew Ayres , Sarah J. Parker , Jennifer E. Van Eyk , Simon K. Lo , Peter Kuhn , Stephen J. Pandol","doi":"10.1016/j.canlet.2025.217546","DOIUrl":"10.1016/j.canlet.2025.217546","url":null,"abstract":"<div><div>Metastatic pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with limited efficacious therapeutic options. Recent investigations have provided proof of concept that circulating tumor cells (CTCs) are reduced by purification of PDAC patient blood samples through ExThera Seraph100™ adsorption filters. Whether additional tumorigenic factors are also removed remains inadequately studied. Here, matched whole blood and purified blood samples from seven PDAC patients were analyzed for microparticle and soluble protein content. For microparticle analysis, patient samples were stratified by abundance. Filters markedly reduced ∼200-nm particles when in high abundance. Exosomes, or vesicles ranging from ∼50 to 150-nm were not significantly affected by the purification process. Proteomic analysis of plasma from the whole and purified blood revealed only a limited number of differentially expressed proteins. The complement C1Q proteins were reduced by the purification process, likely due to their heparin binding affinity. In contrast, there was an elevation in cytoplasmic proteins after purification, which may be due to cell destruction. Taken together, this study shows the selective removal of a subfraction of larger (>200 nm) microvesicles and C1Q during blood purification by the Seraph100™. The clinical significance of these findings requires further study.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217546"},"PeriodicalIF":9.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Artificial intelligence in gastrointestinal cancer research: Image learning advances and applications

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-12 DOI: 10.1016/j.canlet.2025.217555

Shengyuan Zhou , Yi Xie , Xujiao Feng , Yanyan Li , Lin Shen , Yang Chen

{"title":"Artificial intelligence in gastrointestinal cancer research: Image learning advances and applications","authors":"Shengyuan Zhou , Yi Xie , Xujiao Feng , Yanyan Li , Lin Shen , Yang Chen","doi":"10.1016/j.canlet.2025.217555","DOIUrl":"10.1016/j.canlet.2025.217555","url":null,"abstract":"<div><div>With the rapid advancement of artificial intelligence (AI) technologies, including deep learning, large language models, and neural networks, these methodologies are increasingly being developed and integrated into cancer research. Gastrointestinal tumors are characterized by complexity and heterogeneity, posing significant challenges for early detection, diagnostic accuracy, and the development of personalized treatment strategies. The application of AI in digestive oncology has demonstrated its transformative potential. AI not only alleviates the diagnostic burden on clinicians, but it improves tumor screening sensitivity, specificity, and accuracy. Additionally, <span>AI</span> aids the detection of biomarkers such as microsatellite instability and mismatch repair, supports intraoperative assessments of tumor invasion depth, predicts treatment responses, and facilitates the design of personalized treatment plans to potentially significantly enhance patient outcomes. Moreover, the integration of AI with multiomics analyses and imaging technologies has led to substantial advancements in foundational research on the tumor microenvironment. This review highlights the progress of AI in gastrointestinal oncology over the past 5 years with focus on early tumor screening, diagnosis, molecular marker identification, treatment planning, and prognosis predictions. We also explored the potential of AI to enhance medical imaging analyses to aid tumor detection and characterization as well as its role in automating and refining histopathological assessments.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217555"},"PeriodicalIF":9.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Corrigendum to “Lycorine promotes IDH1 acetylation to induce mitochondrial dynamics imbalance in colorectal cancer cells” [Canc. Lett. 573 (2023) 216364]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-09 DOI: 10.1016/j.canlet.2025.217533

Fang-Fang Zhuo , Ling Li , Ting-Ting Liu , Xiao-Min Liang , Zhuo Yang , Yong-Zhe Zheng , Qian-Wei Luo , Jia-Hong Lu , Dan Liu , Ke-Wu Zeng , Peng-Fei Tu

引用次数: 0

CircMFN2/miR-361-3p/ELK1 feedback loop promotes glutaminolysis and the progression of hepatocellular carcinoma

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-09 DOI: 10.1016/j.canlet.2025.217473

Xiaopei Hao , Xiangjun Qian , Chenxi Xie , Zhengzheng Wang , Xiaoqian Wang , Yang Ji , Xiaokai Zhang , Qingjun Li , Baishun Wan , Hong Cui , Li Wang , Nanmu Yang , Liang Qiao , Haibo Yu , Feng Han , Hao Zhuang , Jinxue Zhou

{"title":"CircMFN2/miR-361-3p/ELK1 feedback loop promotes glutaminolysis and the progression of hepatocellular carcinoma","authors":"Xiaopei Hao , Xiangjun Qian , Chenxi Xie , Zhengzheng Wang , Xiaoqian Wang , Yang Ji , Xiaokai Zhang , Qingjun Li , Baishun Wan , Hong Cui , Li Wang , Nanmu Yang , Liang Qiao , Haibo Yu , Feng Han , Hao Zhuang , Jinxue Zhou","doi":"10.1016/j.canlet.2025.217473","DOIUrl":"10.1016/j.canlet.2025.217473","url":null,"abstract":"<div><div>Current evidence indicates that circRNAs are involved in the development of multiple malignancies including hepatocellular carcinoma (HCC). However, the specific functions of circRNAs in HCC metabolism and progression and their underlying regulatory mechanisms remain unclear. We have identified a novel circRNA circMFN2, by bioinformatics analysis of circRNA microarray data from the GEO database. The levels of circMFN2 were assessed in HCC cell lines and tissues, and its clinical relevance was assessed. The effect of circMFN2 on HCC cells was evaluated <em>in vitro</em> and <em>in vivo</em>. The effect of ELK1 on glutaminolysis and HCC progression was also explored. Patients with HCC and high circMFN2 expression exhibited worse survival outcomes. Functionally, downregulation of circMFN2 repressed the proliferation, invasion, and migration of HCC cells <em>in vitro</em>, whereas ectopic expression of circMFN2 had the opposite effects. The effects of tumor enhancement by circMFN2 on HCC were confirmed by <em>in vivo</em> experiments. Mechanistically, circMFN2 acted as a sponge for miR-361-3p, leading to the upregulation of its target ELK1, whereas ELK1 was enriched in the MFN2 promoter to enhance the transcription and expression of MFN2, indirectly leading to the upregulation of circMFN2. Additionally, we found that circMFN2 promotes glutaminolysis in HCC by increasing ELK1 phosphorylation. We concluded that circMFN2 facilitates HCC progression via a circMFN2/miR-361-3p/ELK1 feedback loop, which promotes glutaminolysis mediated by the upregulation of phosphorylated ELK1. Therefore, circMFN2 not only serves as a potential prognostic indicator, but it could also serve as a therapeutic target for HCC. Further studies are warranted.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217473"},"PeriodicalIF":9.1,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Traditional medicine Bazi Bushen potentiates immunosurveillance of senescent liver cancer cells via cGAS-STING signaling activation in macrophages. 传统药物巴子布申能通过激活巨噬细胞中的cGAS-STING信号增强对衰老肝癌细胞的免疫监视。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-08 DOI: 10.1016/j.canlet.2025.217544

Fuxue Xing, Hongwei Lv, Wei Xiang, Liang Wang, Qianni Zong, Guishuai Lv, Chunying Liu, Qiyu Feng, Hongyang Wang, Wen Yang

{"title":"Traditional medicine Bazi Bushen potentiates immunosurveillance of senescent liver cancer cells via cGAS-STING signaling activation in macrophages.","authors":"Fuxue Xing, Hongwei Lv, Wei Xiang, Liang Wang, Qianni Zong, Guishuai Lv, Chunying Liu, Qiyu Feng, Hongyang Wang, Wen Yang","doi":"10.1016/j.canlet.2025.217544","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217544","url":null,"abstract":"<p><p>Senescent cancer cells often evade immune clearance to exert profound effects on cancer progression and therapy resistance. Improving immunosurveillance to eliminate senescent cancer cells is a crucial measure to enhance anti-cancer therapy. Bazi Bushen (BZBS) is a traditional medicine with the function of relieving fatigue and delaying ageing, but its role in tumor treatment remains poorly understood. Herein, we find that BZBS promotes immunosurveillance of both chemotherapy- and oncogene-induced senescent liver cancer cells, further leading to enhanced chemotherapy efficacy and dramatic tumor repression in mice. Mechanistically, BZBS induces mitochondrial DNA leakage by mitochondrial damage to further activate cGAS-STING signaling in macrophages. Subsequently, cGAS-STING signaling activation in macrophages recruits CD8<sup>+</sup> T cells into tumor and promotes the anti-tumor activity of CD8<sup>+</sup> T cells to eradicate senescent cancer cells. Furthermore, host STING is responsible for BZBS-mediated immunosurveillance of senescent liver cancer cells in mice. Therefore, our findings unveil the role of traditional medicine BZBS in activating cGAS-STING signaling and potentiating senescence immunosurveillance to enhance anti-cancer therapy.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217544"},"PeriodicalIF":9.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-08 DOI: 10.1016/j.canlet.2025.217543

Doyeon Kim , Carter A. Allen , Dongjun Chung , Lingbin Meng , Xiaoli Zhang , Wenqing Zhang , Yuli Ouyang , Zihai Li , Feng Hong

{"title":"A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages","authors":"Doyeon Kim , Carter A. Allen , Dongjun Chung , Lingbin Meng , Xiaoli Zhang , Wenqing Zhang , Yuli Ouyang , Zihai Li , Feng Hong","doi":"10.1016/j.canlet.2025.217543","DOIUrl":"10.1016/j.canlet.2025.217543","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment, yet the roles and mechanisms of TAMs in inflammation-associated oncogenesis remain enigmatic. We report that protein canopy homolog 2 (CNPY2) functions as a novel TLR4 regulator, promoting cytokine production in macrophages. CNPY2 binds directly to TLR4. <em>Cnpy</em>2 deficiency reduces cell surface expression of TLR4, nuclear translocation of NFκB and cytokine production in macrophages. Macrophage-specific CNPY2 deficiency significantly decreases cytokine production in macrophages and reduces hepatocarcinogenesis in a diethylnitrosamine (DEN)-induced liver cancer model. RNA-sequencing analysis revealed <em>Cnpy2</em> knockout decreased the mRNA level and cell surface expression of two VEGF receptors, Flt1 and Kdr, compared to those in WT counterparts, resulting in inhibition of macrophage tumor infiltration. <em>Cnpy2</em> knockout inhibits NFκB2/p52-mediated transcription of <em>Flt1</em> and Kdr in macrophages. These findings demonstrate that CNPY2 regulates macrophages in both inflammation and hepatocarcinogenesis and may serve as a therapeutic target for cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217543"},"PeriodicalIF":9.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Unveiling FKBP7 as an early endoplasmic reticulum sentinel in pancreatic stellate cell activation, collagen remodeling and tumor progression

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-07 DOI: 10.1016/j.canlet.2025.217538

Christophe Quemerais , Christine Jean , Alexia Brunel , Emilie Decaup , Guillaume Labrousse , Hippolyte Audureau , Jérôme Raffenne , Ismahane Belhabib , Jérôme Cros , Aurélie Perraud , Nelson Dusetti , Remy Nicolle , Muriel Mathonnet , Stéphane Pyronnet , Yvan Martineau , Marjorie Fanjul , Corinne Bousquet

{"title":"Unveiling FKBP7 as an early endoplasmic reticulum sentinel in pancreatic stellate cell activation, collagen remodeling and tumor progression","authors":"Christophe Quemerais , Christine Jean , Alexia Brunel , Emilie Decaup , Guillaume Labrousse , Hippolyte Audureau , Jérôme Raffenne , Ismahane Belhabib , Jérôme Cros , Aurélie Perraud , Nelson Dusetti , Remy Nicolle , Muriel Mathonnet , Stéphane Pyronnet , Yvan Martineau , Marjorie Fanjul , Corinne Bousquet","doi":"10.1016/j.canlet.2025.217538","DOIUrl":"10.1016/j.canlet.2025.217538","url":null,"abstract":"<div><div>In pancreatic ductal adenocarcinoma (PDAC), fibroblast activation leads to excessive secretion of extracellular matrix (ECM) and soluble factors that regulate tumor progression, prompting investigation into endoplasmic reticulum (ER)-resident proteins that may support this activation. We identified FKBP7, a peptidyl-prolyl isomerase in the ER, as overexpressed in PDAC stroma compared to cancer cells, and in patients with favorable prognosis. Analysis of single-cell RNA sequencing databases revealed FKBP7 expression in pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs). When analyzed by immunohistochemistry on PDAC patient tissues, FKBP7 emerged as an early activation marker in the preneoplastic stroma, preceding αSMA expression, and responding to FAK- and TGFβ-induced stiffening and pro-fibrotic programs in PSCs. Functional analyses revealed that FKBP7 knockdown in PSCs enhanced contractility, Rho/FAK signaling, and secretion of pro-inflammatory cytokines as well as remodeling of type I collagen, promoting an activated phenotype and accelerating tumor growth <em>in vivo</em>. Conversely, FKBP7 expression supported a tumor-restraining (i.e. encapsulating) ECM characterized by type IV collagen. Mechanistically, FKBP7 interacts with BiP, and blocking this interaction instead leads to increased PSC secretion of type I collagen. Thus, FKBP7 serves as a novel PSC marker and ER regulator in a complex with BiP of the secretion of specific collagen subtypes, highlighting its potential to mediate ECM normalization and constrain PDAC tumorigenesis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217538"},"PeriodicalIF":9.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

YTHDF3 drives tumor growth and metastasis by recruiting eIF4B to promote Notch2 translation in breast cancer

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-07 DOI: 10.1016/j.canlet.2025.217534

Hongyu Chen , Linling Lin , Zishan Qiao , Yifei Pei , Yiyang Gao , Kangliang Lou , Lulin Yang , Chengxi Li , Yueyang He , Jingwen Bai , Guojun Zhang

{"title":"YTHDF3 drives tumor growth and metastasis by recruiting eIF4B to promote Notch2 translation in breast cancer","authors":"Hongyu Chen , Linling Lin , Zishan Qiao , Yifei Pei , Yiyang Gao , Kangliang Lou , Lulin Yang , Chengxi Li , Yueyang He , Jingwen Bai , Guojun Zhang","doi":"10.1016/j.canlet.2025.217534","DOIUrl":"10.1016/j.canlet.2025.217534","url":null,"abstract":"<div><div>YTH domain family protein 3 (YTHDF3), an m<sup>6</sup>A RNA reader, is implicated in various cancers, but its role in breast cancer progression and metastasis remains unclear. In this study, we explore the oncogenic potential of YTHDF3 in breast cancer, focusing on its impact on epithelial-mesenchymal transition (EMT) and metastasis. We found that YTHDF3 is significantly upregulated in breast cancer tissues and associated with poor relapse-free survival (RFS). Functional studies demonstrated that YTHDF3 promotes EMT in breast cancer cell lines by enhancing cell migration, invasion, and metastasis <em>in vivo</em>. Mechanistically, we show that YTHDF3 regulates Notch2, a key driver of EMT, through an m<sup>6</sup>A-dependent mechanism. YTHDF3 binds to m<sup>6</sup>A-modified Notch2 mRNA and recruits eIF4B to facilitate its translation, leading to increased Notch2 translation and subsequent inducing EMT. Our findings highlight the importance of the YTHDF3-Notch2 axis in driving EMT and metastasis in breast cancer. Furthermore, targeting YTHDF3 with lipid nanoparticles (LNPs) encapsulating siRNA and indocyanine green (ICG) significantly suppressed tumor growth and lung metastasis while enabling real-time therapeutic monitoring via ICG fluorescence imaging. These findings establish YTHDF3 as a critical driver of EMT and metastasis through m<sup>6</sup>A-dependent Notch2 translation, highlighting its potential as a therapeutic target in breast cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217534"},"PeriodicalIF":9.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Current status and prospects of targeted therapy for cholangiocarcinoma based on molecular characteristics

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-07 DOI: 10.1016/j.canlet.2025.217540

Xiaowen Cui , Teng Huang , Tianyi Jiang , Hongyang Wang

{"title":"Current status and prospects of targeted therapy for cholangiocarcinoma based on molecular characteristics","authors":"Xiaowen Cui , Teng Huang , Tianyi Jiang , Hongyang Wang","doi":"10.1016/j.canlet.2025.217540","DOIUrl":"10.1016/j.canlet.2025.217540","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a serious public health issue due to its insidious onset and dismal prognosis. The past few years have witnessed and highlighted the development of understanding and management of CCA. The combination of gemcitabine and cisplatin (GP) chemotherapy regimen with immunotherapy using immune checkpoint inhibitors has been considered the new standard first-line treatment alternative for advanced CCA. Notably, the proportion of patients with advanced CCA with targetable genetic mutations is approximately 40 %, and these patients may be considered for molecularly targeted therapy in the second-line treatment. In this review, we highlight the advances and progress in targeted therapies for advanced CCA, with special attention to data from Asian populations, including Chinese. In addition, we present in detail the phosphatase tension homolog (PTEN), a novel biomarker for both of first-line chemotherapy and second-line targeted therapy in advanced CCA, and its ability to forecast prognosis in patients with CCA. The mechanisms of rapid resistance to targeted agents warrant further investigation and address in light of the development of new targeted therapies. Precision medicine is gradually playing an increasing role in achieving optimal therapeutic outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"614 ","pages":"Article 217540"},"PeriodicalIF":9.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SQLE amplification accelerates esophageal squamous cell carcinoma tumorigenesis and metastasis through oncometabolite 2,3-oxidosqualene repressing Hippo pathway.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-07 DOI: 10.1016/j.canlet.2025.217528

Xuesong Liu, Mengzhu Lv, Bicong Feng, Ying Gong, Qingjie Min, Yan Wang, Qingnan Wu, Jie Chen, Dongyu Zhao, Jinting Li, Weimin Zhang, Qimin Zhan

{"title":"SQLE amplification accelerates esophageal squamous cell carcinoma tumorigenesis and metastasis through oncometabolite 2,3-oxidosqualene repressing Hippo pathway.","authors":"Xuesong Liu, Mengzhu Lv, Bicong Feng, Ying Gong, Qingjie Min, Yan Wang, Qingnan Wu, Jie Chen, Dongyu Zhao, Jinting Li, Weimin Zhang, Qimin Zhan","doi":"10.1016/j.canlet.2025.217528","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217528","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide, characterized by a dismal prognosis and elusive therapeutic targets. Dysregulated cholesterol metabolism is a critical hallmark of cancer cells, facilitating tumor progression. Here, using whole genome sequencing data from several ESCC cohorts, we identified the important role of squalene epoxidase (SQLE) in promoting ESCC tumorigenesis and metastasis. Specifically, our findings highlight the significance of 2,3-oxidosqualene, an intermediate metabolite of cholesterol biosynthesis, synthesized by SQLE and metabolized by lanosterol synthase (LSS), as a key regulator of ESCC progression. Mechanistically, the interaction between 2,3-oxidosqualene and vinculin enhances the nuclear accumulation of Yes-associated protein 1 (YAP), thereby increasing YAP/TEAD-dependent gene expression, and accelerating both tumor growth and metastasis. In a 4-nitroquinoline 1-oxide (4-NQO)-induced ESCC mouse model, overexpression of Sqle resulted in accelerated tumorigenesis compared to wild-type controls, highlighting the pivotal role of SQLE in vivo. Furthermore, elevated SQLE expression in ESCC patients correlates with poorer prognoses, suggesting potential therapeutic avenues for ESCC treatment. In conclusion, our study elucidates the oncogenic function of 2,3-oxidosqualene as a naturally occurring metabolite and proposes modulation of its levels as a promising therapeutic strategy for ESCC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217528"},"PeriodicalIF":9.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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