Molecular Cancer最新文献

{"title":"Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy","authors":"Huiru Zhang, Jialiang Fan, Deyang Kong, Yu Sun, Qi Zhang, Renshen Xiang, Shuaibing Lu, Wenjing Yang, Lin Feng, Haizeng Zhang","doi":"10.1186/s12943-025-02460-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02460-1","url":null,"abstract":"Immunometabolism has established a groundbreaking paradigm for cancer immunotherapy by decoding the intricate interaction networks between metabolic pathways and immune responses. This review comprehensively explores the metabolic reprogramming of immune cells in the tumor microenvironment, analyzes the roles of key metabolic pathways, enzymes, and metabolites in immune regulation, and unveils the intricate metabolic interactions between tumor and immune cells. Furthermore, we discuss how metabolic interventions can enhance antitumor immune responses and highlight the potential of immunometabolic checkpoints as therapeutic targets. Future research in immunometabolism will focus on the application of advanced technologies, the discovery of novel metabolic biomarkers, and metabolomics-driven personalized medicine to advance cancer diagnosis, treatment, and precision oncology.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"15 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241862","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":"Microplastics as emerging carcinogens: from environmental pollutants to oncogenic drivers","authors":"Sarvesh Kumar Mishra, Tapojyoti Sanyal, Pritha Kundu, Rupesh Kumar, Dipanjan Ghosh, Gopal Chakrabarti, Nilabja Sikdar, Sayan Bhattacharya, Santanu Paul, Amlan Das","doi":"10.1186/s12943-025-02409-4","DOIUrl":"https://doi.org/10.1186/s12943-025-02409-4","url":null,"abstract":"The widespread environmental pollution of microplastics (MPs) and nanoplastics (NPs) has become a major public health issue, with increasing evidence associating their bioaccumulation with cancer onset. This review offers a thorough examination of the etiological contributions of MPs/NPs in carcinogenesis, clarifying their mechanistic roles in in vitro, in vivo, and patient-derived evidences. Relevant studies were systematically identified and screened following the PRISMA 2020 guidelines to ensure methodological transparency and quality. We highlighted recent discoveries that emphasize the varied accumulation of MPs in several human cancer tissues, including lung, colorectal, gastric, cervical, breast, pancreatic, prostate and penile malignancies. These particles induce harmful biological effects by chronic inflammation, oxidative stress, genotoxicity, disturbance of lipid metabolism, and alteration of the tumor immunological microenvironment. Significantly, MPs/NPs disrupt various oncogenic signaling pathways, particularly NF-κB, PI3K/Akt/mTOR, Wnt/β-catenin, and p53, therefore facilitating tumor initiation, development, and metastasis. In vitro and in vivo studies have corroborated the carcinogenic potential of MPs/NPs, illustrating their capacity to cause cellular transformation, augment metastatic characteristics, and modify drug resistance pathways in cancer cells. Furthermore, the detection of MPs in human biological matrices, including blood, placenta, and tumor tissues, highlights direct human exposure and potential systemic effects. This review emphasizes the mechanistic insights with therapeutic significance, addressing current knowledge gaps in the field. Future research must prioritize biomarker identification, patient-centered investigations, therapeutic targeting, and the formulation of regulatory policies to alleviate the health hazards linked to microplastic exposure. Understanding the intricate relationship between MPs/NPs and cancer biology could facilitate the development of novel cancer prevention and management strategies related to environmental contamination.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"77 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241864","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":"Emerging role of cancer-associated fibroblasts in the premetastatic niche","authors":"Shuaixi Yang, Ying Guo, Jiachi Jia, Wenming Cui, Xinhao Zhang, Yuhang Wang, Zhiyuan Xie, Yingshuai Fang, Xianfei Ding, Lei Chang, Ying Liu","doi":"10.1186/s12943-025-02461-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02461-0","url":null,"abstract":"In recent years, tumor metastasis has become one of the major causes of high recurrence and mortality in cancer patients. Owing to multiorgan involvement, metastatic cancers are now clinically difficult to cure and often have a very poor prognosis. In recent years, an increasing number of studies have shown that the establishment of a premetastatic niche (PMN) is necessary for tumor metastasis. Cancer-associated fibroblasts (CAFs), which are closely related to tumor development, are deeply involved in regulating PMN establishment. By regulating EVs, metabolism and other pathways, CAFs actively shape microenvironmental characteristics, including inflammation, angiogenesis, increased vascular permeability, lymphangiogenesis, immunosuppression and extracellular matrix (ECM) remodeling. With the development of single-cell sequencing technology, our understanding of the role and significance of heterogeneous CAFs in the PMN has improved. Multiple therapeutic strategies targeting CAFs in the PMN have also been developed. This article focuses on the crosstalk of different subtypes of CAFs with other stromal cells, the mechanisms by which CAFs of different origins mediate PMN formation, and the emerging cancer therapeutic strategies by which CAFs have been targeted in recent years.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"209 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241861","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":"MALAT1 as a molecular driver of tumor progression, immune evasion, and resistance to therapy","authors":"Amirreza Bitaraf, Alireza Zafarani, Pardis Jahandideh, Benyamin Hakak-Zargar, Atousa Haghi, Golareh Asgaritarghi, Sadegh Babashah","doi":"10.1186/s12943-025-02415-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02415-6","url":null,"abstract":"Long noncoding RNAs (lncRNAs) are emerging as important regulators of gene expression in both normal biological systems and disease. Among them, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has attracted considerable attention due to its high nuclear expression and evolutionary conservation. It was first identified as a biomarker for lung cancer metastasis, but since then, its involvement has been reported in a wide range of cancers. MALAT1 influences several key cancer-related processes, including cell proliferation, migration, angiogenesis, apoptosis, epithelial–mesenchymal transition, and the behavior of cancer stem cells. In this review, we take a closer look at how MALAT1 functions through different mechanisms, such as regulating RNA splicing, altering chromatin states, acting as a sponge for microRNAs, or modifying protein interactions, to drive these changes. We also discuss its growing role in shaping the immune landscape of tumors, particularly its involvement in immune evasion, inflammatory signaling, and regulation of immunogenic cell death. In addition, MALAT1 contributes to resistance against therapy, rewiring of cellular metabolism, and communication between tumor and stromal cells via exosomes. While many studies describe MALAT1 as an oncogene, others suggest it may also play a suppressive role depending on the cancer type and biological context. Here, we aim to offer a comprehensive overview of MALAT1’s diverse actions and evaluate its potential as a diagnostic marker and therapeutic target in cancer.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"136 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228738","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":"Circulating tumor cells: mechanisms and clinical significance in colorectal cancer metastasis","authors":"Xuanyu Ren, Mei Song, Xianzhi Liu, Weiling He","doi":"10.1186/s12943-025-02465-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02465-w","url":null,"abstract":"Tumors are a major global health problem. As economic development and material standards increase, the incidence and mortality of digestive system tumors have shown an overall rising trend. Among them, colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death worldwide. Despite advances in molecular biology and therapeutic strategies, tumor metastasis remains the main driver of cancer-related deaths (about 90%). Especially in CRC, the progression of metastasis greatly limits clinical intervention options. Circulating tumor cells (CTCs), a key mediator of hematogenous metastasis, have emerged as a key target for unravelling metastatic mechanisms and developing therapeutic strategies, and are gradually gaining prominence in tumor biology and precision medicine. Therefore, a comprehensive understanding of CTC-mediated mechanisms, especially in the invasion-metastasis cascade of CRC and other cancers of the digestive system, is crucial for early metastasis detection, prevention and identification of new therapeutic targets.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"13 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210017","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":"Non-coding RNAs in gastric cancer: mechanisms and therapeutic prospects","authors":"Zhifei Han, Wenjuan Liu, Yigao Zhu, Yinggang Sun, Dong Sun, Ruyue Jia, Yanting Yang, Houbao Qi, Long Zhang, Yanfei Huo, Nasha Zhang, Jie Chai, Ming Yang","doi":"10.1186/s12943-025-02467-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02467-8","url":null,"abstract":"Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. It is associated with high molecular and phenotypic heterogeneity. Early-stage gastric cancer can be treated with endoscopic resection and surgery, whereas at its advanced stage, sequential chemotherapy presents the only treatment option, which starts with first-line platinum and fluoropyrimidine-based dual drugs, supporting a median survival period of less than one year. Targeted monoclonal antibodies approved for the treatment of gastric cancer are effective for a limited subset of patients. Furthermore, painless and precise markers for the early detection of gastric cancer and new targets for its treatment are unavailable. Interestingly, many non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play key roles in the development of gastric cancer. Multiple pieces of evidence suggest that ncRNAs play a crucial role in the treatment of gastric cancer using chemotherapy and targeted therapy drugs. In this article, we systematically reviewed the important roles of ncRNAs in chemotherapy resistance, immune escape, metabolism, and angiogenesis of gastric cancer, and systematically elucidated the relevant molecular mechanisms. In addition, we also proposed the potential clinical significance of ncRNA as a new therapeutic target and prognostic biomarker for gastric cancer.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"19 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209979","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 circRNA promotes esophageal squamous cell carcinoma progression by inhibiting TRIM25-mediated degradation of IGF2BP family members","authors":"Shuangyan Tan, Yue Ming, Jiawei Guo, Wenrong Liu, Hulin Ma, Yu Liu, Zhijie Xu, A-Lai Gu-Ha, Lunzhi Dai, Yi-Dan Lin, Yong Peng","doi":"10.1186/s12943-025-02442-3","DOIUrl":"https://doi.org/10.1186/s12943-025-02442-3","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. While circular RNAs (circRNAs) are frequently dysregulated in ESCC, their functional roles and molecular mechanisms in tumor progression remain largely unexplored. We characterized circRNA using RT-PCR, Sanger sequencing, and fluorescent in situ hybridization. Gain- and loss-of-function studies in vitro and in vivo were performed to assess circRNA function. Molecular interactions were investigated via RNA pull-down assays coupled with mass spectrometry, electrophoretic mobility shift assays, co-immunoprecipitation, and immunoblot analysis. Clinical relevance was evaluated by RT-qPCR and immunohistochemistry in patient specimens. We identified circLNF, a novel circRNA derived from the long non-coding RNA FIRRE gene, which is significantly upregulated in ESCC. Functional assays demonstrated that circLNF promotes proliferative and migratory capacities in cultured cells and accelerates tumor progression and metastasis in animal models. Mechanistically, circLNF directly interacts with IGF2BP family proteins through their “CAUC” motifs, protecting them from TRIM25-mediated ubiquitination and proteasomal degradation. Importantly, circLNF expression positively correlated with IGF2BP1 protein levels in ESCC patient tissues, underscoring the clinical relevance of the circLNF-IGF2BP axis in ESCC progression. Our findings reveal an oncogenic role of circLNF in ESCC by inhibiting TRIM25-mediated proteasomal degradation of IGF2BP proteins and highlight circLNF as a potential therapeutic target for ESCC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"97 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209953","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":"BRD9-p53-E2F1 circuit orchestrates cell growth and DNA damage repair in gastric cancer","authors":"Qingqing Zhou, Qi Wang, Yantao Duan, Chi Zhang, Tengfei Liu, Hengrui Liu, Mindi Zhao, Zhihuang Hu","doi":"10.1186/s12943-025-02449-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02449-w","url":null,"abstract":"BRD9 is involved in multiple physiological and pathological pathways, yet its functional role and molecular mechanisms in gastric cancer (GC) remain largely unexplored. Addressing this knowledge gap is critical given the persistent global mortality burden of GC and the limited efficacy of current therapeutic strategies. BRD9 expression in GC patients was systematically analyzed using immunohistochemical (IHC) assays and transcriptomic datasets. Comprehensive functional validation, employing cellular and murine tumor models, elucidated BRD9’s role in GC progression. Molecular pathways underlying BRD9-mediated gastric carcinogenesis were delineated through integrated approaches, including RNA sequencing, co-immunoprecipitation (co-IP), subcellular fractionation, and luciferase reporter assays. BRD9 was significantly overexpressed in GC and associated with poor patient prognosis. Functionally, BRD9 promoted GC cell proliferation and enhanced DNA damage repair capacity. Mechanistically, elevated BRD9 expression inhibited p53 nuclear translocation via direct binding, subsequently activating the E2F transcription factor family. Notably, we identified that E2F1 directly bound to and transactivated the BRD9 promoter, establishing a positive feedback loop that sustains BRD9 expression. Additionally, BRD9 knockdown sensitized GC cells to cisplatin and oxaliplatin treatment. These findings highlight the critical role of BRD9 in GC progression and its therapeutic potential. The BRD9-p53-E2F1 axis acts as a crucial regulator of GC cell proliferation and DNA damage response. Targeting BRD9 pharmacologically could be a novel therapeutic approach to enhance chemotherapy efficacy and improve treatment outcomes in GC patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"79 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203103","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":"P23 acts as a negative regulator of ferroptosis in NSCLC by blocking GPX4 degradation via chaperone-mediated autophagy","authors":"Junlin Chen, Yulin Peng, Meirong Zhou, Yilin Che, Shilei Zhao, Chengjian He, Wen Zhang, Xiangge Tian, Wenhao Zhang, Zhe Liu, Minghao Zhou, Guobiao Liang, Xiaokui Huo, Yan Wang, Zhenlong Yu, Xiaochi Ma","doi":"10.1186/s12943-025-02439-y","DOIUrl":"https://doi.org/10.1186/s12943-025-02439-y","url":null,"abstract":"Ferroptosis has been identified as a tumor-inhibiting event in a variety of cancers; however, its molecular basis in non-small cell lung cancer (NSCLC) has not been completely elucidated. Notably, glutathione peroxidase 4 (GPX4) plays a crucial role in ferroptosis. Our previous research revealed that prostaglandin E synthase 3 (p23), a potential transcription factor, plays a crucial role in promoting cancer progression and metastasis through succinylation. Our study revealed a previously unknown antiferroptotic function of p23. Mechanistically, p23 stabilizes GPX4 by competitively binding heat shock cognate 71 kDa protein (HSC70) to suppress chaperone-mediated autophagy (CMA) activity, which subsequently inhibits ferroptosis and accelerates tumor growth. Notably, impairing p23 succinylation disrupts its interaction with HSC70, restoring CMA-mediated GPX4 degradation. Collectively, our findings suggest that targeting p23-regulated CMA pathways represents a potentially viable strategy to modulate ferroptosis in NSCLC. The role of p23 in competing with GPX4 for binding to HSC70, blocking CMA-mediated degradation of GPX4 and inhibiting ferroptosis ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202993","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 immune microenvironment of pathogen-associated cancers and current clinical therapeutics","authors":"Xiao-Yu Wei, Hui-Jing Feng, Ying-Yin Zhu, Shi-Jing Guo, Hong Wang, Ming Li, Qi Mei","doi":"10.1186/s12943-025-02448-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02448-x","url":null,"abstract":"Pathogen-associated cancers account roughly 15–20% of all malignancies worldwide and arise from chronic infections by oncogenic viruses, bacteria and parasites. Pathogens can alter the tumor microenvironment (TME) into an immune-suppressive niche using multiple mechanisms, including immune checkpoint manipulation, chronic inflammation, metabolic reprogramming, and direct epigenetic modifications. Immune dysfunctions related to infections linked to cancers can include M2-polarized macrophages, expansion of MDSCs, exhausted T/NK cells, and tolerogenic dendritic cells, all progressing immune evasion and resistance to cancer therapy. Advances in therapeutics exist in prophylactic vaccines, immune checkpoint inhibitors, and next-generation methods such as the engineered Salmonella to deliver to hypoxic tumors and the targeting the microbiome. The advancement of pathogen-, cancer-, and patient-specific therapeutics is not without its challenges, including heterogeneity of the pathogens, absence of clinically useful biomarkers, concerns about the safety of the restoring anti-pathogen immunity and challenges of scale for manifold interventions. This review will provide a synthesis of the mechanistic aspects of pathogen-mediated TME remodeling, contemporary clinical therapeutics, and ongoing investigations into using pathogen/host dynamics to enhance measurable precision immunotherapy strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"99 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202995","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}