Cancer letters最新文献

{"title":"Cell differentiation-related signaling pathways in hepatocellular carcinoma metastasis","authors":"Ze Xiang ,&nbsp;Jiarui Li ,&nbsp;Yunyang Xu ,&nbsp;Chenhao Xu ,&nbsp;Shusen Zheng ,&nbsp;Jian Chen ,&nbsp;Xuyong Wei ,&nbsp;Xiao Xu","doi":"10.1016/j.canlet.2025.217846","DOIUrl":"10.1016/j.canlet.2025.217846","url":null,"abstract":"<div><div>Primary liver cancer is the third leading cause of cancer-related deaths worldwide, with persistently high incidence and mortality rates. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, has a complex pathogenesis. Moreover, due to the low rate of early diagnosis and limited treatment options, the prognosis for HCC patients is poor, with a median overall survival of approximately one year for advanced-stage HCC. Cancer metastasis is one of the main reasons for HCC-related deaths. During the metastatic process, tumor cells undergo a series of complex biological changes, including epithelial-mesenchymal transition, extracellular matrix remodeling, angiogenesis, and resistance to anoikis, which are key steps. These changes promote the invasion and migration of tumor cells and are central mechanisms of cancer progression. In the metastatic process of HCC, signaling pathways that regulate cell proliferation, differentiation, and apoptosis, such as Hippo-YAP/TAZ, Wnt/β-catenin, Notch, Hedgehog and JAK/STAT, become dysregulated and play a promoting role in the aggressive growth and distant migration of HCC cells. Treatment strategies targeting these pathways are currently being developed. These new agents, being more targeted, may have better tolerability and fewer adverse effects. This review focuses on the role of these key signaling pathways in the metastatic process of HCC and summarizes the treatment strategies targeting these pathways.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217846"},"PeriodicalIF":9.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204028","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":"The role of 7-dehydrocholesterol in inducing ER stress and apoptosis of head and neck squamous cell carcinoma","authors":"Bok-Soon Lee ,&nbsp;Yea-In Park ,&nbsp;Hengtian Liu ,&nbsp;Sang Gyu Kim ,&nbsp;Hyo Jeong Kim ,&nbsp;Ji-Hye Choi ,&nbsp;Si Hyun Rho ,&nbsp;Joselyn Padilla ,&nbsp;Jin Roh ,&nbsp;Hyun Goo Woo ,&nbsp;Hae Jin Seo ,&nbsp;Man Ho Choi ,&nbsp;Yu-Jin Jeong ,&nbsp;Evan C. Lien ,&nbsp;Syed Hassan Mehdi ,&nbsp;Dongjoon Lee ,&nbsp;Donghoon Yoon ,&nbsp;Chul-Ho Kim ,&nbsp;Jiyoung Lee","doi":"10.1016/j.canlet.2025.217842","DOIUrl":"10.1016/j.canlet.2025.217842","url":null,"abstract":"<div><div>Alterations of metabolic pathways that sustain cancer cell survival often offer promising therapeutic avenues. Here, we show that enhanced <em>de novo</em> cholesterol biosynthesis is crucial for the survival of head and neck squamous cell carcinoma (HNSCC). Transcriptomic analysis of HNSCC tissues identified profound dysregulation in steroid and cholesterol metabolism compared to normal tissues. Inhibition of two key enzymes, DHCR7 and DHCR24, which mediate cholesterol biosynthesis, induced apoptosis in HNSCC cells, even when cholesterol levels were restored. Metabolomic profiling revealed the accumulation of 7-dehydrocholesterol (7-DHC) upon DHCR7 or DHCR24 inhibition, triggering endoplasmic reticulum (ER) stress and promoting further cell death. These findings suggest that HNSCC cells adapt to ER stress by modulating 7-DHC levels through enhancing DHCR7 and DHCR24 levels, highlighting a metabolic vulnerability in HNSCC and demonstrating a direct link between cholesterol metabolism and ER stress in cancer cell viability.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217842"},"PeriodicalIF":9.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207817","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":"Corrigendum to \"Targeting mitochondrial ribosomal protein expression by andrographolide and melatonin for colon cancer treatment\" [Cancer Lett. 619 (2025) 1-11 217647].","authors":"Advaitha Midde, Navpreet Arri, Tibor Kristian, Suprabhat Mukherjee, Parth Sarthi Sen Gupta, Yuji Zhang, Mariuz Karbowski, Jaylyn Waddell, Maharajan Nagarajan, Michal Zalzman, Aditi Banerjee","doi":"10.1016/j.canlet.2025.217784","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217784","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217784"},"PeriodicalIF":9.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246617","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":"Structural and material basis of neuron–glioma interactions","authors":"Jun Wang ,&nbsp;Tian-hua Shen ,&nbsp;Jie Liu ,&nbsp;Qian Wen ,&nbsp;Xian-yan Yang ,&nbsp;Yun Deng ,&nbsp;Jiang-jie Duan ,&nbsp;Shi-cang Yu","doi":"10.1016/j.canlet.2025.217843","DOIUrl":"10.1016/j.canlet.2025.217843","url":null,"abstract":"<div><div>The intricate interplay between neurons and gliomas has emerged as an important area of investigation in glioma biology. Accumulating evidence underscores that structural and material alterations constitute the fundamental basis of neuron‒glioma interactions and their pathological consequences. This review comprehensively examines the mechanisms underlying these interactions, with a particular emphasis on specialized structures that facilitate neuron‒glioma communication, including synapses, cell surface ion channels, and tumor microtubules (TMs). In addition to classical neurotransmitters, we highlight the exchange of cytokines, proteins, and extracellular vesicles (EVs) between these cell types. By synthesizing current research findings, this review establishes a conceptual framework for developing innovative therapeutic strategies targeting neuron‒glioma interfaces, offering new perspectives for glioma treatment approaches.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217843"},"PeriodicalIF":9.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191552","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":"Lactylation in tumor microenvironment and immunotherapy resistance: New mechanisms and challenges","authors":"Wenlong Zhu ,&nbsp;Chang Fan ,&nbsp;Yizhuo Hou,&nbsp;Yanjie Zhang","doi":"10.1016/j.canlet.2025.217835","DOIUrl":"10.1016/j.canlet.2025.217835","url":null,"abstract":"<div><div>Tumor microenvironment (TME) is a highly intricate and variable system. The Warburg effect has made researchers further realize that TME is a highly hypoxic microenvironment. Currently, it is reported that lactate is not merely a metabolic waste but also serves important biological functions, which provides a large number of reaction substrates for lactylation. Post-translational modification (PTM) is crucial for signaling and physiological regulation in both normal and cancer cells. Various PTMs play pathological roles in tumor proliferation, metabolism, and the remodeling of the tumor immunosuppressive microenvironment (TIME). Lactylation, as a newly reported PTM, plays an important role in shaping TIME and aggravating tumor immunotherapy resistance. Numerous studies have demonstrated that histone lactylation can directly stimulate gene transcription within chromatin, thereby contributing to tumor promotion and diminishing the efficacy of therapeutic agents against tumors. Advancements in multi-omics technology enable researchers to investigate lactylation-related substrates more effectively. By precisely targeting these sites, it is possible to reduce histone lactylation in order to mitigate their effects on tumor immune resistance. Despite the existence of numerous studies, there remains a notable deficiency of systematic reviews in this field. Therefore, this review focuses on the novel mechanisms of lactylation that promote tumor progression and its impact on tumor immune resistance. Finally, we propose relevant therapeutic regimens for reversing lactylation to guide tumor combined therapy, thus providing benefits upon more patients with tumor immune resistance.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217835"},"PeriodicalIF":9.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186566","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":"Improved survival in pancreatic ductal adenocarcinoma: Exciting promise of multimodal management strategies.","authors":"Murray Korc, Min Li","doi":"10.1016/j.canlet.2025.217828","DOIUrl":"10.1016/j.canlet.2025.217828","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217828"},"PeriodicalIF":9.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180098","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":"Formation of polyploid giant cancer cells and the transformative role of human cytomegalovirus IE1 protein.","authors":"Ranim El Baba, Sandy Haidar Ahmad, Caroline Vanhulle, Laure Vreux, Estelle Plant, Carine Van Lint, Georges Herbein","doi":"10.1016/j.canlet.2025.217824","DOIUrl":"10.1016/j.canlet.2025.217824","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) infection has been linked to various cancers, including glioblastoma (GB), breast cancer (BC), and ovarian epithelial cancer (OC) especially high grade serous ovarian cancer (HGSOC). HCMV gene products control tumorigenic cellular pathways and processes associated with all the hallmarks of cancer. Among the suspected HCMV proteins involved in cellular transformation, the immediate early-1 (IE1) protein stands out as a significant player. Herein, we presented the experimental evidence supporting HCMV-IE1 role as a reprogramming factor that induces the transformation of human ovarian epithelial cells (OECs) resulting in the generation of \"CMV transformed ovarian epithelial cells-IE1″ or CTO-IE1. These transformed cells exhibit similarities to those previously reported by our group, following infection with the high-risk oncogenic HCMV strain DB. HCMV-IE1-DB protein triggered distinct cellular and molecular mechanisms in stably transduced OECs. This included downregulation of Rb/p53 and upregulation of Myc/EZH2, concurrent with the emergence of polyploid giant cancer cells (PGCCs) and giant cell cycling in the culture. HCMV-IE1-DB silencing limited cellular transformation and stemness. In HGSOC, PGCCs were detected in the presence of IE1; the latter positively correlated with Myc. In addition, HCMV IE1 exhibits transforming capabilities in human mammary epithelial cells (HMECs) and human astrocytes (HAs) in vitro, reflecting its potential role in the transformation observed in vivo. This highlights the tumorigenic properties of Myc/EZH2 in the context of IE1-mediated transformation parallel to PGCCs appearance.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217824"},"PeriodicalIF":9.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172969","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":"Anti-tumor effects on tumor-infiltrating natural killer cells by localized ablative immunotherapy and immune checkpoint inhibitors: An integrated and comparative study using scRNAseq analysis","authors":"Kaili Liu ,&nbsp;Ashley R. Hoover ,&nbsp;Yuanhong Sun ,&nbsp;Trisha I. Valerio ,&nbsp;Coline Furrer ,&nbsp;Jacob Adams ,&nbsp;Lin Wang ,&nbsp;Abdul Rafeh Naqash ,&nbsp;Wei R. Chen","doi":"10.1016/j.canlet.2025.217825","DOIUrl":"10.1016/j.canlet.2025.217825","url":null,"abstract":"<div><div>Localized ablative immunotherapy (LAIT), a combination of photothermal therapy (PTT) and the immunostimulant glycated chitosan (GC), has demonstrated therapeutic efficacy in cancer treatment. However, its impact on the tumor microenvironment (TME), particularly on tumor-infiltrating natural killer (TINK) cells, remains to be fully elucidated. Using single-cell RNA sequencing (scRNAseq), we analyzed the transcriptional and functional modulations of TINK cells by LAIT in a mouse breast cancer model. Additionally, we investigated immune checkpoint inhibitor (ICI)-induced changes in NK cells across multiple cancer types and evaluated the clinical relevance of these transcriptional changes using The Cancer Genome Atlas (TCGA) database. ScRNAseq revealed five NK cell subtypes, with LAIT increasing the proportion of interferon-enriched NK cells and enhancing NK cell differentiation and cytotoxicity. Functional analyses demonstrated that LAIT upregulated activation, cytotoxic, and interferon pathway genes while downregulating immune-suppressive genes, effects largely driven by GC. Comparative analysis showed significant transcriptional overlap between ICI and LAIT, highlighting shared pathways in NK cell-mediated cytotoxicity and chemokine signaling. Prognostic models constructed from ICI- and LAIT-induced gene signatures effectively stratified breast cancer patients by survival risk, with LAIT-induced genes showing the highest predictive performance. Furthermore, higher NK cell proportions and the expression of key prognostic genes, such as PSME2, IGKC, and KLRB1, were associated with improved overall survival. LAIT and ICIs enhance NK cell-mediated antitumor responses via distinct yet complementary mechanisms, emphasizing their potential for synergistic use. These findings provide novel insights into NK cell modulation within the TME and support the development of combinatorial immunotherapy strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217825"},"PeriodicalIF":9.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147857","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":"CDC34 suppresses macrophage phagocytic activity and predicts poor response to immune checkpoint inhibitor in cancers","authors":"Xiao-Liang Jie ,&nbsp;Jia-Cong Wei ,&nbsp;Di Wang ,&nbsp;Xiang-Wei Zhang ,&nbsp;Meng-Yao Lv ,&nbsp;Yong-Fang Lin ,&nbsp;Yi-Shuai Tan ,&nbsp;Zheng Wang ,&nbsp;Aikede Alifu ,&nbsp;Lei Ji ,&nbsp;Yu-Ke Shen ,&nbsp;Cong Wang ,&nbsp;Bing-Qing Xu ,&nbsp;Zheng Liu ,&nbsp;Si-Chong Han ,&nbsp;Zi-Hao Wang ,&nbsp;Xiao-Wan Tong ,&nbsp;Lin Feng ,&nbsp;Jian-Ming Ying ,&nbsp;Guang-Biao Zhou ,&nbsp;Gui-Zhen Wang","doi":"10.1016/j.canlet.2025.217822","DOIUrl":"10.1016/j.canlet.2025.217822","url":null,"abstract":"<div><div>The Cell Division Cycle 34 (CDC34) is an E2 ubiquitin-conjugating enzyme that is required for proteasomal degradation of substrate proteins, and is able to stabilize proteins including the epidermal growth factor receptor to promote lung carcinogenesis. Here, we conducted a pan-cancer analysis of CDC34 in The Cancer Genome Atlas datasets, and found its high expression in breast cancer and negative association with patient outcomes. Analysis of single-cell RNA-sequencing data revealed a negative role of CDC34 in macrophage phagocytotic activity for cancer cells. CDC34 stabilized hypoxia-inducible factor 1α (HIF1α) and transcriptionally upregulated CD47 in cancer cells to evade phagocytosis by macrophages. Inhibition of CDC34 inhibited tumor growth and synergized with anti-PD-L1 antibody in murine models. CDC34 was positively associated with CD47 and negatively associated with CD8⁺ granzyme B⁺ T-cell infiltration in patient samples, and patients with co-overexpression of CDC34 and CD47 had markedly poorer prognosis compared to those with high expression of either marker alone. In pre-treatment tumor samples, non-responders to immunotherapy exhibited significantly higher CDC34 levels and reduced CD8⁺ T-cell infiltration compared to responders. These findings indicated that CDC34 is critical to immune evasion and could be a potential therapeutic target for those resistant to immune checkpoint inhibitors.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217822"},"PeriodicalIF":9.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149260","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":"Therapeutic targeting of circTNK2 with nanoparticles restores tamoxifen sensitivity and enhances NK cell-mediated immunity in ER-positive breast cancer","authors":"Runxin Wu ,&nbsp;Shubin Yu ,&nbsp;Aiwei Bi ,&nbsp;Yingliang Li ,&nbsp;Deanna Tiek ,&nbsp;Kuai Yu ,&nbsp;Haiwei Xiong ,&nbsp;Qingfeng Shi ,&nbsp;Zhaohong Mo ,&nbsp;Xiaozhou Yu ,&nbsp;Xiao Song ,&nbsp;Fang Yin ,&nbsp;Yu Wang ,&nbsp;Wang Yi ,&nbsp;Mengting Liu ,&nbsp;Penghui Li ,&nbsp;Bo Hu ,&nbsp;Aiping Le ,&nbsp;Shi-Yuan Cheng ,&nbsp;Boxuan Zhou","doi":"10.1016/j.canlet.2025.217823","DOIUrl":"10.1016/j.canlet.2025.217823","url":null,"abstract":"<div><div>Endocrine resistance is a leading cause of relapse in patients with estrogen receptor (ER)-positive breast cancer (ER⁺ BC), with tamoxifen resistance being the most prevalent form. circTNK2, a circular RNA, is overexpressed in tamoxifen-resistant BC tissues and is correlated with poor prognosis. circTNK2 encodes a novel 487-amino acid protein, termed C-TNK2-487aa, which inhibits the recruitment of natural killer (NK) cells into BC tumors. Mechanistically, C-TNK2-487aa interacts with STAT3 and promotes STAT3 phosphorylation (p-STAT3) in ER⁺ BC cells. The increased p-STAT3 competes with STAT1 binding, inhibiting the formation of STAT1 homodimers that induces CXCL10 expression, ultimately leading to immune evasion. Additionally, circTNK2 RNA binds to SRSF1 and promotes tamoxifen resistance and BC tumorigenicity by activating AKT-mTOR signaling. Delivery of BC-targeting ZIF-8 nanoparticles loaded with circTNK2 antisense oligonucleotides (ASOs) and a CXCL10-encoding plasmid DNA markedly suppresses the growth of BC tumor xenografts, restores tamoxifen sensitivity, and increases CD56⁺ NK cell infiltration into BC tumors. Our data describe a critical role of the circTNK2-encoded peptide and its RNA in ER⁺ BC resistance to tamoxifen and immune evasion, providing a therapeutic vulnerability in treating tamoxifen-resistant breast cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217823"},"PeriodicalIF":9.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149286","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}