Journal of Experimental & Clinical Cancer Research最新文献

{"title":"ECM-Induced IL-23 Drives Immune Suppression in Breast Cancer via Regulating PD-1 on Tregs.","authors":"Giovanna Talarico, Mara Lecchi, Anna Zanichelli, Paola Portararo, Laura Botti, Vera Cappelletti, Massimo Costanza, Annamaria Piva, Pietro Pratesi, Francesco Bertolini, Massimo Di Nicola, Claudio Tripodo, Valeria Cancila, Serenella Maria Pupa, Mario Paolo Colombo, Claudia Chiodoni, Paolo Verderio, Sabina Sangaletti","doi":"10.1186/s13046-025-03518-0","DOIUrl":"10.1186/s13046-025-03518-0","url":null,"abstract":"<p><strong>Background: </strong>High-grade breast cancer (HGBC) is an aggressive disease with poor prognosis, underscoring the need for new treatment strategies. The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a pivotal role in tumor progression, therapy resistance, and immune regulation. An ECM-related gene signature (defined ECM3), found in approximately 35% of HGBC cases, is associated with aggressive tumors, epithelial-to-mesenchymal transition (EMT), poor clinical outcome and increased infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs).</p><p><strong>Methods: </strong>In this study, we investigated the impact of the ECM on T cell regulation in HGBC patients, focusing on the relationship between ECM3 + tumors and T cell phenotypes. We employed mouse models to dissect the molecular mechanisms linking ECM components to T cell regulation, with particular attention to the role of the matricellular protein SPARC, a key component of the ECM3 signature.</p><p><strong>Results: </strong>We revealed a significant correlation between highly suppressive programmed cell death-1 (PD-1) negative regulatory T cells (Tregs) and ECM3 + tumors. In mouse models, SPARC was found to down-regulate PD-1 on Tregs by promoting IL-23 release, which in turn induced SATB1 expression, a repressor of the pdcd1 gene. The selective expression of the IL-23 receptor on Tregs accounted for the targeted effect of IL-23 on these cells. Notably, blocking IL-23 with monoclonal antibodies restored PD-1 expression on Tregs and activated T effector cells.</p><p><strong>Conclusion: </strong>These findings extend the immune-regulatory role of the ECM to include regulatory T cells and identify potential new therapeutic targets for high-grade breast cancers. Moreover, they highlight ECM3 as a potential biomarker of resistance to PD-1/PD-L1 immune checkpoint blockade (ICB), suggesting that ECM3⁺ patients may benefit from alternative checkpoint inhibitor therapies beyond PD-1/PD-L1.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"264"},"PeriodicalIF":12.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977243","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}

{"title":"Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.","authors":"Lu Liu, Weijun Wan, Yilin Chang, Luoquan Ao, Yan Xu, Xiang Xu","doi":"10.1186/s13046-025-03527-z","DOIUrl":"10.1186/s13046-025-03527-z","url":null,"abstract":"<p><p>The tumor microenvironment (TME) of breast cancer is a complex ecosystem, in which cancer-associated fibroblasts (CAFs), as the most abundant stromal cell type, meticulously construct an ecological niche that supports tumor growth through mechanisms including extracellular matrix (ECM) remodeling, secretion of bioactive factors, and interactions with neighboring cells. High-resolution technologies, including single-cell sequencing and spatial transcriptomics, have revealed the high heterogeneity, functional diversity, and spatial distribution within the CAF population. Significant differences exist in the interactions between distinct CAF subpopulations and immune cells. Through complex crosstalk with the immune system, they collaboratively establish an immunosuppressive network, becoming a core driving force for tumor immune escape. This review focuses on the latest research advances in heterogeneous subpopulations of CAFs within the breast cancer microenvironment, delves into how the complex bidirectional crosstalk between different CAF subpopulations and immune cells collaboratively shapes the tumor immune microenvironment (TIME), and summarizes various CAF-based therapeutic strategies for breast cancer, aiming to provide critical theoretical basis and novel therapeutic perspectives for the clinical translation of CAF heterogeneity research.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"263"},"PeriodicalIF":12.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977221","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}

{"title":"E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.","authors":"Jingyuan Li, Yiyu Chen, Jianyu Wang, Liyuan Liu, Javeria Qadir, Dan Xie, Xue Wan, Yanan Luo, Jiawen Xian, Ting Ye","doi":"10.1186/s13046-025-03506-4","DOIUrl":"https://doi.org/10.1186/s13046-025-03506-4","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a predominant subtype of non-small cell lung adenocarcinoma (NSCLC). It is typically asymptomatic and associated with high mortality rates. Despite recent advancements in screening technologies and therapeutic approaches, its pathogenesis still remains elusive. Therefore, it is imperative to explore new diagnostic markers and therapeutic targets for LUAD management. Cancer stem cells (CSCs) have high self-renewal capacity and incur therapeutic resistance, thus, considered as crucial elements in initiating and promoting tumor development. Contextual to this, the present study reveals the role of the transcriptional activator E2F1 in LUAD oncogenesis and its association with various biological characteristics of lung cancer stem cells (LCSCs). Whereby, it may also serve as a crucial factor in regulating autophagy. Autophagy can modulate stemness by either promoting or inhibiting CSCs characteristics. Pertinently, our study integrated bioinformatics, in-vitro and in-vivo experiments to elucidate that E2F1 can induce ALDH1A1 through autophagy, thus promoting self-renewal and drug resistance of LCSCs, as well as tumorigenicity. Mechanistically, \"E2F1-autophagy-ALDH1A1\" axis enhanced the self-renewal capacity and drug resistance of LCSCs in a p53-dependent manner, highlighting the potential of E2F1 as a promising marker for LUAD.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"261"},"PeriodicalIF":12.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977177","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}

{"title":"Investigating the role of UBASH3B in cancer: structural relevance, physiological functions, and therapeutic possibilities.","authors":"Sophie Werner, Cameron Westlake, Madeleine Ndahayo, Ishita Gupta, Daria A Gaykalova","doi":"10.1186/s13046-025-03511-7","DOIUrl":"https://doi.org/10.1186/s13046-025-03511-7","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally and presents a persistent clinical challenge due to the limited availability of effective targeted therapeutics. Recent studies have identified the ubiquitin-associated and SH3 domain-containing B (UBASH3B), a tyrosine phosphatase, as a key oncogenic player in HNSCC pathogenesis. Elevated UBASH3B expression correlates with poor clinical outcomes in HNSCC patients. Mechanistically, UBASH3B promotes tumor progression by stabilizing the epidermal growth factor receptor (EGFR) levels, thereby enhancing downstream signaling pathways that promote cancer cell proliferation, survival, and therapeutic resistance. In this review, we provide a comprehensive overview of the structural features and physiological functions of UBASH3B, along with a focused discussion on its emerging role in HNSCC tumorigenesis. We further explore the potential of targeting UBASH3B as a novel therapeutic target, underscoring its promise in reshaping treatment paradigms. Elucidating the molecular functions of UBASH3B in HNSCC may uncover new vulnerabilities and pave the way for the development of novel therapeutic strategies that target its activity.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"262"},"PeriodicalIF":12.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977296","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}

{"title":"Bufalin inhibits hepatocellular carcinoma progression by blocking EGFR-mediated RAS-RAF-MEK-ERK pathway activation.","authors":"Jingwen Liu, Jia Jiang, Ju Huang, Zhi-E Fang, Lexi Liu, Yong Liu, Weiqi Nian, Jianyuan Tang, Zhilei Wang","doi":"10.1186/s13046-025-03531-3","DOIUrl":"10.1186/s13046-025-03531-3","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains one of the most challenging malignancies with persistently dismal long-term survival outcomes despite multidisciplinary advances in diagnostic and therapeutic strategies. Cinobufacini preparations have garnered increasing attention as adjunctive therapeutic agents in integrated management strategies for HCC. Bufalin (BF), the active ingredient in Cinobufacini, has garnered substantial attention due to its potent antitumor effects. However, the precise molecular mechanisms underlying its antitumor actions remain incompletely characterized.</p><p><strong>Methods: </strong>A clinical retrospective cohort analysis was conducted to establish the definitive clinical benefit of Cinobufacini in improving treatment outcomes among HCC patients. Building upon these clinical insights, a multi-dimensional approach was implemented to elucidate the anti-HCC molecular mechanisms mediated by the bioactive component BF of Cinobufacini.</p><p><strong>Results: </strong>Western medical treatment combined with Cinobufacini shows an improving trend in the overall survival (OS) and progression free survival (PFS) of HCC patients. Moreover, our exploratory analysis suggests a potential dose-response relationship where longer cumulative exposure to Cinobufacini appears to be associated with improved clinical outcomes. In vitro experiments demonstrated that BF significantly inhibited cell viability and proliferation, and induced apoptosis in HepG2 and HCCLM3. Network pharmacology analysis identified 20 core targets, and molecular docking revealed high-affinity binding between BF and key proteins, including EGFR, GRB2, SRC, and MAPK1. HCC tissue microarrays confirmed the overexpression of EGFR and GRB2 in HCC tissues. Further mechanistic investigations revealed that BF suppressed the EGFR-mediated RAS/RAF/MEK/ERK pathway activation in HepG2 and HCCLM3. BF intervention significantly reduced tumor volumes in C57BL/6 mouse subcutaneous HCC xenograft and BALB/c Nude mouse orthotopic HCC xenograft models. Moreover, BF inhibited the phosphorylation levels of EGFR, RAF, MEK, and ERK in tumor tissues, further corroborating its inhibitory effects on the RAS/RAF/MEK/ERK signaling pathway.</p><p><strong>Conclusions: </strong>Our observational data suggest a potential association between Cinobufacini use and favorable trends in OS and PFS among HCC patients. BF exerts its antitumor effects against HCC by interfering with the EGFR-mediated RAS/RAF/MEK/ERK signaling pathway. These findings not only elucidate the molecular mechanisms underlying the antitumor actions of BF but also highlight the potential of Cinobufacini preparations as a valuable therapeutic option for HCC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"260"},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977066","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}

{"title":"PD-1⁺ NK cell subsets in high grade serous ovarian cancer: an indicator of disease severity and a target for combined immune-checkpoint blockade.","authors":"Marco Greppi, Giovanna Tabellini, Ornella Patrizi, Valentina Obino, Matteo Bozzo, Mariangela Rutigliani, Franco Gorlero, Martina Di Luca, Laura Paleari, Ombretta Melaiu, Michele Paudice, Fabrizio Loiacono, Patrizio Castagnola, Valerio Gaetano Vellone, Pascale André, Domenico Mavilio, Gianluca Ubezio, Simona Candiani, Camilla Jandus, Lorenzo Moretta, Andrea De Censi, Daniel Olive, Simona Sivori, Eric Vivier, Fabio Rampinelli, Silvia Parolini, Silvia Pesce, Emanuela Marcenaro","doi":"10.1186/s13046-025-03508-2","DOIUrl":"https://doi.org/10.1186/s13046-025-03508-2","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"258"},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977328","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}

{"title":"RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.","authors":"Arturo Orlacchio, Yasuko Kajimura, Lara Rizzotto, Anna Tessari, Shimaa H A Soliman, Rosa Visone, Liwen Zhang, Brian Fries, Lino Tessarollo, Joseph Amann, David P Carbone, Alessia Lodi, Amer Ahmed, Ruggiero Gorgoglione, Giuseppe Fiermonte, Mike Freitas, Dario Palmieri, Jacob Kaufman, Vincenzo Coppola","doi":"10.1186/s13046-025-03491-8","DOIUrl":"https://doi.org/10.1186/s13046-025-03491-8","url":null,"abstract":"<p><strong>Background: </strong>RANBP9 and RANBP10, also called Scorpins, are essential components of the C-terminal to LisH (CTLH) complex, an evolutionarily conserved poorly investigated multisubunit E3 ligase. Their role in non-small cell lung cancer (NSCLC) is unknown.</p><p><strong>Methods: </strong>In this study, first we used stable loss-of function and overexpression inducible cell lines to investigate the ability of either RANBP9 or RANBP10 to form their own functional CTLH complex. Then, we probed lysates from patient tumors and analyzed data from publicly available repositories to investigate the expression of RANBP9 and RANBP10. Finally, we used inducible cell lines in vitro to recapitulate the expression observed in patients and investigate the changes of the proteome and the ubiquitylome associated with either RANBP9 or RANBP10 in NSCLC.</p><p><strong>Results: </strong>Here, we show that the two Scorpins are both expressed in NSCLC cells and that either of them can independently support the formation of the CTLH complex. Short-term experiments revealed that the RANBP9 and RANBP10 proteins balance each other in terms of expression, and the acute overexpression of one or the other results in significant reshaping of the NSCLC cell proteome and ubiquitylome. A higher RANBP9/RANBP10 ratio is associated with greater proliferation in both NSCLC cell lines and patients. Acute increased expression of RANBP10 slows NSCLC cell proliferation and decreases the level of proliferation-associated proteins, including key players in DNA replication.</p><p><strong>Conclusions: </strong>We present evidence that the Scorpins act as partial antagonists and work together as one sophisticated rheostat to modulate the CTLH complex ubiquitylation output, which regulates cell proliferation and other key biological processes in NSCLC. These results suggest that the two Scorpins can be considered as targets for the treatment of NSCLC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"259"},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975898","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}

{"title":"TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells.","authors":"Francesca Scantamburlo, Alessia Rubini, Margherita Toffanin, Maria Egle Castorina, Francesco Ciscato, Sofia Tomasoni, Paolo Finotti, Ranieri Verin, Valentina Zappulli, Marco Fantuz, Camilla Bean, Andrea Rasola, Ionica Masgras","doi":"10.1186/s13046-025-03525-1","DOIUrl":"https://doi.org/10.1186/s13046-025-03525-1","url":null,"abstract":"<p><strong>Background: </strong>Metabolic adaptations can sustain the pro-neoplastic functions exerted by macrophages in the tumor microenvironment. Malignant peripheral nerve sheath tumors (MPNSTs), aggressive and incurable sarcomas that develop either sporadically or in the context of the genetic syndrome Neurofibromatosis type 1, are highly infiltrated by macrophages, whose contribution to MPNST growth remains poorly characterized. Here, we analyze the role played by the molecular chaperone TRAP1, a regulator of mitochondrial metabolic pathways, in shaping the pro-tumoral activity of macrophages associated to MPNST cells.</p><p><strong>Methods: </strong>We have studied the phenotypic changes elicited by a MPNST cell-conditioned medium in macrophages with or without TRAP1, and their subsequent ability to support MPNST cell growth and migration and endothelial cell angiogenesis.</p><p><strong>Results: </strong>The presence of TRAP1 is required in both naive and M2-like macrophages for eliciting phenotypic changes that lead to the acquisition of pro-neoplastic features. TRAP1-expressing macrophages become able to sustain MPNST cell growth and migration and to exert pro-angiogenic properties on endothelial cells through accumulation of the metabolite succinate and the ensuing activation of a HIF-1α-dependent transcriptional program.</p><p><strong>Conclusions: </strong>Our data provide evidence of a molecular crosstalk between MPNST cellular components, in which soluble factors released by cancer cells drive phenotypic changes in macrophages that in turn enhance pro-tumoral biological routines in both MPNST and endothelial cells. TRAP1-dependent metabolic rewiring in macrophages is mandatory for sustaining this interplay, as a TRAP1-succinate-HIF-1α signaling axis orchestrates their acquisition of tumor-promoting features.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"257"},"PeriodicalIF":12.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976325","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}

{"title":"CDKN2A deletion is associated with immune desertification in diffuse pleural mesothelioma.","authors":"Federica Torricelli, Benedetta Donati, Veronica Manicardi, Mila Gugnoni, Francesca Reggiani, Gloria Manzotti, Pierluigi Di Chiaro, Cristian Ascione, Simonetta Piana, Riccardo Valli, Roberto Piro, Massimiliano Paci, Nicola Facciolongo, Filippo Lococo, Alessia Ciarrocchi","doi":"10.1186/s13046-025-03522-4","DOIUrl":"https://doi.org/10.1186/s13046-025-03522-4","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse Pleural Mesothelioma (DPM) is a rare and incurable cancer. Immune checkpoint inhibitors (ICIs) marked some advances but only for a limited fraction of patients. Improving response prediction to ICIs is currently a clinical need in DPM. Deletion of CDKN2A gene, in chr9p21.3, is one of the most frequent alterations in DPM. As in other settings, deletion of CDKN2A locus has been associated with an immunosuppressive phenotype. Here we investigated the consequences of CDKN2A deletion (CDKN2Adel) on the tridimensional organization and function of immune infiltrate in DPM.</p><p><strong>Methods: </strong>A retrospective cohort of 89 DPMs was analyzed and assessed for CDKN2Adel through digital droplet PCR. Immune-profiling was assessed by analyzing 770 immune-related genes by digital profiling. Finally, morphologically resolved, high-dimensional transcriptomic approach was used to reconstruct the spatial architecture of immune-tumor interaction in wild-type and deleted FFPE samples.</p><p><strong>Results: </strong>CDKN2Adel was detected in 41.5% of DPMs and was associated with reduced survival (p = 0.04). Bulk gene expression identified 373 differentially expressed genes, of which 98.6% were downregulated in CDKN2Adel samples. These genes were enriched in several immune categories, suggesting significant immune deprivation in deleted tumors. Deconvolution analysis confirmed a major depletion of infiltrating immune cells including effector populations. Spatial transcriptomics revealed that this immunosuppressive phenotype was different according to histotype and prominent in the sarcomatoid lesions.</p><p><strong>Conclusion: </strong>These data demonstrated that CDKN2Adel deeply affects the spatial organization of immune microenvironment by depleting immune-signaling and reducing or preventing immune infiltration, supporting the potential implementation of this alteration as ICIs predictive biomarker in DPM.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"256"},"PeriodicalIF":12.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977159","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}

{"title":"A novel SOX6 + melanoma cell subtype promotes early microsatellite invasion in Asian acral melanoma through fatty acid transport disorder.","authors":"Chuan Lv, Kexin Chen, Tengjiao Wang, Junfeng Jiang, Guanghui Hu, Jianan Gu, Tao Liu, Sheng Wang, Haiying Dai, Yue Wang","doi":"10.1186/s13046-025-03516-2","DOIUrl":"https://doi.org/10.1186/s13046-025-03516-2","url":null,"abstract":"<p><p>Acral melanoma (AM) is the predominant subtype of melanoma in Asians. Early detection and prevention can significantly improve patient outcomes; however, there is a lack of effective early biomarkers for predicting AM metastasis. Here, we employed single-cell and spatial transcriptomics analyses to investigate early microsatellite lesions of AM and identify biomarkers of invasiveness in these lesions. Our results characterize a highly immunosuppressive microenvironment and metabolic process shifts in early AM microsatellite lesions that promote the metastatic potential. The transcription factor SOX6 is overexpressed in microsatellite lesions and marks a population of highly invasive melanoma cells. The pro-invasive role of overexpressed SOX6 was validated in vivo and in vitro, including its ability to enhance tumor invasion by upregulating cellular glycolysis, disrupt fatty acid transport, and increase intracellular phosphatidylcholine content. This study suggests that SOX6-overexpressing melanoma cells are the main driver subpopulation promoting early invasion of AM and establishes SOX6 and fatty acid transport processes as biomarkers and potential therapeutic targets for early melanoma metastasis.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"254"},"PeriodicalIF":12.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977082","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}