Cancer letters最新文献

{"title":"Corrigendum to “CXCR2/CXCL5 axis contributes to epithelial-mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling” [Cancer Lett. 358 2015 Pages 124–135]","authors":"Shao-Lai Zhou , Zheng-Jun Zhou , Zhi-Qiang Hu , Xun Li , Xiao-Wu Huang , Zheng Wang , Jia Fan , Zhi Dai , Jian Zhou","doi":"10.1016/j.canlet.2025.217927","DOIUrl":"10.1016/j.canlet.2025.217927","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"630 ","pages":"Article 217927"},"PeriodicalIF":10.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728112","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}

{"title":"ECD co-operates with ERBB2 to promote tumorigenesis through upregulation of unfolded protein response and glycolysis.","authors":"Benjamin B Kennedy, Mohsin Raza, Sameer Mirza, Asher Rajkumar Rajan, Farshid Oruji, Matthew M Storck, Subodh M Lele, Timothy E Reznicek, Lusheng Li, M Jordan Rowley, Shibiao Wan, Bhopal C Mohapatra, Hamid Band, Vimla Band","doi":"10.1016/j.canlet.2025.217959","DOIUrl":"10.1016/j.canlet.2025.217959","url":null,"abstract":"<p><p>The ecdysoneless (ECD) mRNA and protein are overexpressed in breast cancer (BC), correlating with poor prognosis and shorter patient survival, particularly in ERBB2/HER2-positive BC. This study investigates the co-operative oncogenic mechanism of ECD and ERBB2 by deriving transgenic mice overexpressing ECD and/or ERBB2 (huHER2) in mammary epithelium under the MMTV promoter, as well as immortal human mammary epithelial cell lines (hMECs) overexpressing ECD and/or ERBB2. While the tumor latency and percentage of mice with tumors were similar between single and double-transgenic mice, we observed more and larger tumors in double transgenic mice in comparison to ECD or huHER2 single transgenic mice. Compared to huHER2Tg mice, which developed more homogenous solid nodular carcinomas, double transgenic mice (ECD;huHER2Tg) developed heterogenous and histologically aggressive mammary tumors with basal-like phenotype and epithelial mesenchymal transition (EMT) features, as seen in ECDTg mice and those reported in patients. ECD and ERBB2 overexpressing hMECs showed significant increase in oncogenic traits as compared to single gene expressing cells. Transcriptomic analysis revealed upregulation of two major oncogenic pathways, unfolded protein response (UPR) and glycolysis in ECD;huHER2Tg tumors as well as in ECD + ERBB2-overexpressing hMECs. ECD + ERBB2-overexpressing hMECs exhibited an increase in glucose uptake and enhanced glycolytic rate as compared to ECD or ERBB2-overexpressing hMECs. ECD as an RNA binding protein directly associated with mRNAs of three key glycolytic enzymes (LDHA, PKM2 and HK2) and mRNA of a major UPR regulated gene HSPA5, and increased mRNA stability. Knockdown of these genes resulted in decreased oncogenic traits of ECD + ERBB2 overexpressing hMECs. Taken together, our findings support a co-operative role of ECD and ERBB2 in oncogenesis by enhancing two major oncogenic pathways, UPR and glycolysis.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217959"},"PeriodicalIF":10.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752504","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}

{"title":"O-GlcNAcylation of YBX1 drives a glycolysis-histone lactylation feedback loop in hepatocellular carcinoma","authors":"Yang Ji ,&nbsp;Zhenggang Xu ,&nbsp;Lei Tang ,&nbsp;Tianyu Huang ,&nbsp;Xiaoxin Mu ,&nbsp;Chuangye Ni ,&nbsp;Bai Tang ,&nbsp;Hao Lu ,&nbsp;Chuanyong Zhang ,&nbsp;Shikun Yang ,&nbsp;Xuehao Wang","doi":"10.1016/j.canlet.2025.217957","DOIUrl":"10.1016/j.canlet.2025.217957","url":null,"abstract":"<div><div>Metabolic reprogramming is a hallmark of tumorigenesis and progression, with alterations in glucose metabolism, often referred to as the Warburg effect, playing a central role. This shift allows tumor cells to rapidly acquire energy and generate essential metabolic intermediates, thereby supporting enhanced growth. Despite its significance, the mechanisms by which tumor cells upregulate glycolysis remain inadequately understood. In this study, we report that YBX1 is highly expressed in hepatocellular carcinoma (HCC) and is closely associated with glycolysis. We show that YBX1 is modified by O-linked N-acetylglucosamine (O-GlcNAc) at threonine 57 (T57), which stabilizes the protein and increases its expression. This modification also promotes the phosphorylation of YBX1 at serine 102, facilitating its nuclear translocation. Consequently, this process enhances the transcription of glycolysis-related genes and stimulates lactate production. Moreover, YBX1 activates the transcription of P300, which in turn drives the lactylation of histones, particularly H3K18la. Cleavage Under Targets and Tagmentation (CUT&amp;Tag) analysis reveals that H3K18 lactylation positively regulates YBX1 gene transcription. Our findings establish a positive feedback loop involving YBX1, glycolysis, and H3K18 lactylation that accelerates HCC progression. Disrupting this feedback loop may provide a novel therapeutic strategy for HCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217957"},"PeriodicalIF":10.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720770","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}

{"title":"OTUD3-mediated stabilization of SLC7A11 drives sunitinib resistance by suppressing ferroptosis in clear cell renal cell carcinoma","authors":"Tian Xu ,&nbsp;Huimin Liu ,&nbsp;Neng Ling ,&nbsp;Daiquan Chen ,&nbsp;Jing Dai ,&nbsp;Wenjing Chen ,&nbsp;Yuxuan Li ,&nbsp;Xirong Gao ,&nbsp;Wei Zhai ,&nbsp;Mao Ye ,&nbsp;Yang Sun ,&nbsp;Weihong Tan","doi":"10.1016/j.canlet.2025.217942","DOIUrl":"10.1016/j.canlet.2025.217942","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC), as the main type of RCC was treated with tyrosine kinase inhibitor (TKI) at the late stage. While drug resistance is the main challenge for TKIs like sunitinib, and the underline mechanisms remain unclear. Here, we found that OTUD3 is over-expressed in ccRCC and promotes sunitinib resistance in tumor cells. OTUD3 deubiquitinates the cystine/glutamate transporter SLC7A11 and protect it from proteasome degradation, which promotes cystine transport into cells and reduces intracellular ROS levels, thereby inhibiting sunitinib-induced ferroptosis. Our findings suggest that targeting OTUD3 could be a potential strategy to enhance ferroptosis and improve the therapeutic efficacy of sunitinib in ccRCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217942"},"PeriodicalIF":10.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724693","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}

{"title":"Neoadjuvant immune checkpoint inhibition improves protection against hepatic melanoma metastasis","authors":"Sebastian A. Wohlfeil ,&nbsp;Céline Weller ,&nbsp;Bianca Dietsch ,&nbsp;Dennis Alexander Agardy ,&nbsp;Tamara Boschert ,&nbsp;Sheila A. Vormehr ,&nbsp;Christof Dormann ,&nbsp;Niklas Straub ,&nbsp;Verena Häfele ,&nbsp;Michael Platten ,&nbsp;Sergij Goerdt ,&nbsp;Cyrill Géraud","doi":"10.1016/j.canlet.2025.217950","DOIUrl":"10.1016/j.canlet.2025.217950","url":null,"abstract":"<div><h3>Background</h3><div>Liver metastasis of cutaneous melanoma (CM) correlates with a decreased response to immune checkpoint inhibition (ICI). Here, we investigated whether neoadjuvant ICI protects against liver metastasis to prevent the development of therapy resistances.</div></div><div><h3>Methods</h3><div>A stage II CM was modeled by intracutaneous injections of WT31 or B16F10 <em>luc2</em> melanoma cells. Combined ICI (anti-PD-1/anti-CTLA-4) was applied in murine models of hepatic melanoma metastasis comparing neoadjuvant or adjuvant regimens. Immune cell composition and responses in the liver and CMs were comparatively analyzed by scRNA-Seq, flow cytometry, immunofluorescence, <em>in situ</em> hybridization and multiplex cytokine assays.</div></div><div><h3>Results</h3><div>Neoadjuvant ICI resulted in improved protection against liver metastasis in comparison to adjuvant therapy. This superior response was associated with an expansion of T cells in CMs, the peripheral blood and the liver. An increased expression of T_H1-associated markers and a downregulation of T_H2-associated markers were detected in T cells from CMs and livers of mice by scRNA-Seq and immunofluorescence after neoadjuvant ICI. Analysis of hepatic cytokines also revealed lower levels of T_H2-associated IL-4 and of IL-15.</div></div><div><h3>Conclusion</h3><div>Our data demonstrate that neoadjuvant ICI provides superior protection against hepatic melanoma metastasis with a shift towards an anti-tumor T_H1 immune response. Therefore, neoadjuvant ICI is a promising therapeutic option for CM to prevent the development of organ-specific therapy resistance mechanisms.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217950"},"PeriodicalIF":10.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717615","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}

{"title":"Radiotherapy in combination with PD-1 and TIGIT blockade mediate antitumor abscopal effects and immune memory via CD8+ T cells","authors":"Chunsheng Wang ,&nbsp;Linzhi Han ,&nbsp;Jianguo Zhang ,&nbsp;Qian Ji ,&nbsp;Xiuli Guo ,&nbsp;Yangyi Li ,&nbsp;Siqi Li ,&nbsp;Jingyi He ,&nbsp;Fajian He ,&nbsp;Weijing Dai ,&nbsp;Minghuan Li ,&nbsp;Jinming Yu ,&nbsp;Dawei Chen ,&nbsp;Yan Gong ,&nbsp;Conghua Xie","doi":"10.1016/j.canlet.2025.217935","DOIUrl":"10.1016/j.canlet.2025.217935","url":null,"abstract":"<div><div>This study investigated the synergistic antitumor effects of radiotherapy combined with <em>anti</em>-PD-1 and <em>anti</em>-TIGIT antibodies (aPD-1/aTIGIT), focusing on primary and abscopal tumor control, immune mechanisms, and long-term immune memory. Using bilateral subcutaneous tumor models (LLC, CMT-167, B16-F10, MC38) in C57/BL6 mice, we demonstrated that triple therapy (radiotherapy + aPD-1 + aTIGIT) significantly enhanced tumor regression and systemic antitumor responses. Flow cytometry, multicolor immunofluorescence, and single-cell transcriptomics revealed that triple therapy amplified CD8⁺ T cell activation, reversed exhaustion, and increased tumor infiltration. M1 macrophages exhibited robust immune activation and enhanced interactions with CD8⁺ T cells, driven by upregulated NF-κB, STAT1, and chemokine pathways. Longitudinal Luminex cytokine profiling identified sustained increases in TNF-α, CXCL10, and CCL5 post-treatment, supporting macrophage-T cell crosstalk. Rechallenge experiments and adoptive CD8⁺ T cell transfers confirmed that triple therapy generated durable central memory CD8⁺ T cells, which mediated antigen-specific immune memory and prevented tumor recurrence. These findings establish CD8⁺ T cells as central mediators of abscopal effects and long-term immunity, highlighting the critical role of M1 macrophage polarization in amplifying therapeutic synergy. By elucidating the mechanisms underlying resistance to PD-1 monotherapy, this study provides a translatable strategy to enhance clinical outcomes through radiotherapy-immunotherapy combinations.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217935"},"PeriodicalIF":9.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711123","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}

{"title":"A splicing alternative of REST in neuroendocrine neoplasms of the lung and breast","authors":"Yang-Yang Kong ,&nbsp;Zheng Wang ,&nbsp;Yi-Meng Zhang ,&nbsp;Fen-Rong Xie ,&nbsp;Lin Feng ,&nbsp;Zheng Liu ,&nbsp;Yong-Fang Lin ,&nbsp;Gui-Zhen Wang ,&nbsp;Guang-Biao Zhou","doi":"10.1016/j.canlet.2025.217947","DOIUrl":"10.1016/j.canlet.2025.217947","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"633 ","pages":"Article 217947"},"PeriodicalIF":10.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717614","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}

{"title":"Technological innovations promote cancer stem cell-based translational research","authors":"Zijiao Yang ,&nbsp;Wenyu Liao ,&nbsp;Weizhong Wang ,&nbsp;Wengui Shi ,&nbsp;Zuoyi Jiao ,&nbsp;Zuoren Yu","doi":"10.1016/j.canlet.2025.217949","DOIUrl":"10.1016/j.canlet.2025.217949","url":null,"abstract":"<div><div>Cancer remains one of the leading causes of death worldwide, with therapy resistance and tumor recurrence driven by a subpopulation of cells known as cancer stem cells (CSCs). CSCs possess a remarkable ability to evade apoptosis, adapt to harsh microenvironments, regenerate tumors, and exhibit metabolic flexibility along with enhanced DNA repair mechanisms. The tumor microenvironment (TME) plays a critical role in supporting CSCs. Stromal cells, extracellular matrix components, and hypoxic niches provide both physical and biochemical support, promoting CSC survival and resistance to therapy. Recent advancements in techniques, such as single-cell sequencing, functional genomics, organ chip platforms, and artificial intelligence (AI), have enabled a deeper understanding of the molecular regulatory mechanisms governing CSCs, and facilitated the development of targeted interventions. This article provides a comprehensive overview and prospectives of CSC-based therapeutic strategies benefiting from technological developments.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217949"},"PeriodicalIF":9.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711276","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}

{"title":"Phosphorylation of MSX1 controls tumorigenesis and bone development through targeting FBXW7 degradation","authors":"Yenan Yang ,&nbsp;Xiang Jia ,&nbsp;Yu Peng ,&nbsp;Sihong Lu ,&nbsp;Chen Wang ,&nbsp;Heng Zhang ,&nbsp;Xuefei Wang ,&nbsp;Qiang Zhou ,&nbsp;Yihong Sun ,&nbsp;Gang Wang","doi":"10.1016/j.canlet.2025.217948","DOIUrl":"10.1016/j.canlet.2025.217948","url":null,"abstract":"<div><div>The transcription factor MSX1, typically expressed in early development but not in most adult tissues, is often re-activated in various cancers, although its underlying oncogenic mechanisms remain elusive. Here, we found that MSX1 promotes the degradation of FBXW7, an E3 ligase and tumor suppressor, through the CDK1-mediated phosphorylation of MSX1 at Ser136. The phosphorylation mimic MSX1 S136D mutant, but not the dephosphorylated S136A mutant, degrades FBXW7 and results in the accumulation of its substrates, including c-MYC and MCL1, ultimately leading to gastric cancer growth and resistance to apoptosis. As the pMSX1–FBXW7 oncogenic axis was validated in clinical gastric cancer samples, we then developed a therapeutic strategy combining chemotherapy with CDK1 inhibition, which synergistically inhibited the gastric cancer growth. Remarkably, the generated S136A knock-in mouse model showed significant protection against carcinogen-induced gastric tumorigenesis, while also exhibited defective limb and skull dysraphism. Collectively, these findings unraveled the importance of pMSX1–FBXW7 axis for both cancer and mammalian development.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217948"},"PeriodicalIF":9.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711124","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}

{"title":"YY1-glycolytic axis promotes high glucose-induced cancer stemness in endometrial cancer: A multi-omics guided therapeutic strategy","authors":"Xiao Yang ,&nbsp;Chengcheng Li ,&nbsp;Yuan Cheng ,&nbsp;Shaojie Qin ,&nbsp;Lingpu Zhang ,&nbsp;Ling Zhou ,&nbsp;Jingyi Zhou ,&nbsp;Haihua Xiao ,&nbsp;Yu Bai ,&nbsp;Jianliu Wang","doi":"10.1016/j.canlet.2025.217936","DOIUrl":"10.1016/j.canlet.2025.217936","url":null,"abstract":"<div><div>Abnormal glucose metabolism in patients with diabetes mellitus or hyperglycaemia is a key factor leading to poor prognosis of endometrial cancer (EC) and warrants further exploration of its underlying mechanisms. In this study, we employed an integrative multiomics approach, including proteomics, transcriptomics, nontargeted metabolomics and single-cell metabolomics, and revealed that high glucose promotes EC cell stemness, thereby promoting tumour progression and reducing the sensitivity of EC cells to cisplatin (platinum-Pt^II). Mechanistically, there is a significant association between enhanced stemness and increased glycolytic activity in EC cells, and the transcription factor YY1 was found to be a key regulator of PDK1, CD133, and CD44 under high-glucose conditions, with YY1 binding to their promoter regions. Inhibiting YY1 expression effectively attenuates the stem cell properties of tumour cells and increases their sensitivity to cisplatin. Furthermore, we developed ROS-responsive nanoparticles for the codelivery of C8-Pt^IV-COOH and YY1 siRNA (NP-Pt^IV/siYY1), which synergistically amplify antitumour effects and chemosensitivity in patient-derived xenograft (PDX)-bearing mice with diabetes. Taken together, our results demonstrated that YY1 is a promising therapeutic target for inhibiting EC stemness and overcoming chemoresistance, particularly under high-glucose conditions.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217936"},"PeriodicalIF":10.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717616","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}