Neoplasia最新文献

{"title":"Cell type composition in bulk prostate cancer tissue is a prognostic biomarker","authors":"Xiaokang Zhang ,&nbsp;Bjarne Johannessen ,&nbsp;Susanne G. Kidd ,&nbsp;Mari Bogaard ,&nbsp;Ane Stranger ,&nbsp;Ulrika Axcrona ,&nbsp;Karol Axcrona ,&nbsp;Rolf I. Skotheim","doi":"10.1016/j.neo.2026.101272","DOIUrl":"10.1016/j.neo.2026.101272","url":null,"abstract":"<div><div>Prostate cancer, among the most prevalent cancer types globally, exhibits marked heterogeneity and varying disease progression and clinical outcomes. Improved molecular subtyping is needed for patient stratification. Since prostate cancer has relatively few somatic point mutations, whole-transcriptome data instead offers a rich and relevant source of molecular data. We analyzed bulk tissue transcriptomes from four cohorts to characterize primary prostate cancer’s cell type composition. A deconvolution of cell types was performed based on gene expression profiles. Patients with available multi-sample regional data from different tumor foci were analyzed for intrapatient heterogeneity. Three cell type composition subtypes were defined: T cells enriched (TCE), epithelial cells enriched (EPCE), and tumor-associated stromal cells enriched (TASCE). A machine learning model was developed to classify these subtypes and validated in three independent cohorts. The subtyping demonstrated a high correlation with established clinicopathological parameters (e.g., Gleason score, p-value &lt; 0.05), and the classifier showed a promising ability to predict biochemical recurrence. Moreover, our analysis revealed that interfocal heterogeneity in patients with multifocal cancer significantly surpassed intrafocal heterogeneity (p-value &lt; 0.05). In conclusion, this study provides a novel prostate cancer subgrouping based on cell type composition, with the TASCE subtype significantly associated with high biochemical recurrence risk.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101272"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A calcium-sensing MCTP1/FYN/MEF2C circuit drives therapy-induced neuroendocrine prostate cancer","authors":"Phan Vu Thuy Dung ,&nbsp;Wei-Yu Chen ,&nbsp;Ming-Kun Liu ,&nbsp;Shauh-Der Yeh ,&nbsp;Gagan Kajla ,&nbsp;Hsiu-Lien Yeh ,&nbsp;Wei-Hao Chen ,&nbsp;Kuo-Ching Jiang ,&nbsp;Han-Ru Li ,&nbsp;Cheng-Sheng Chen ,&nbsp;Himisha Beltran ,&nbsp;Yu-Ching Wen ,&nbsp;Yen-Nien Liu","doi":"10.1016/j.neo.2025.101251","DOIUrl":"10.1016/j.neo.2025.101251","url":null,"abstract":"<div><div>Neuroendocrine prostate cancer (NEPC) represents a highly aggressive, treatment‑refractory phenotype that frequently emerges after androgen‑deprivation therapy (ADT). Although perturbed calcium signaling has been implicated in prostate cancer bone metastasis, the specific molecular mechanisms governing NEPC progression remain incompletely characterized. Here, we delineate the MCTP1/FYN/MEF2C signaling axis as a pivotal modulator of intracellular calcium homeostasis that drives neuroendocrine differentiation (NED) and enhances tumor aggressiveness. We demonstrate that ADT upregulates MCTP1, a transmembrane protein with calcium-sensing capabilities, which subsequently activates the Src-family kinase FYN to initiate oncogenic signaling cascades. This activation induces transcriptional upregulation of bone morphogenesis-related genes, including <em>MEF2C</em> and <em>ALPL</em>. Mechanistically, calcium-responsive transcription factors ZEB1 and ZEB2 directly transactivate <em>MEF2C</em>, thereby integrating calcium flux with epithelial-to-mesenchymal transition (EMT) programs in prostate cancer. Elevated ZEB1/ZEB2-dependent MEF2C expression reinforces the MCTP1/FYN kinase pathway, potentiating neuroendocrine lineage commitment and ALPL enzymatic activity. Chromatin immunoprecipitation coupled with transcriptomic analyses reveals that MEF2C directly occupies regulatory elements of <em>MCTP1, FYN,</em> and <em>ALPL</em>, enabling their calcium-dependent transcriptional activation. Structure-based virtual screening identified a potent small-molecule antagonist targeting MCTP1, which markedly attenuates tumor burden, ALPL activity, and neuroendocrine marker expression in prostate cancer in vitro and in vivo models. Collectively, these findings establish MCTP1 as a novel therapeutically exploitable vulnerability in therapy-induced NEPC, providing critical insights into the calcium-dependent oncogenic signaling networks mediated by the MCTP1/FYN/MEF2C axis in advanced prostate cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101251"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis unveils tumor heterogeneity and immunotherapy predictive model in breast cancer for precision medicine and early detection","authors":"Zhenxiong Zhao ,&nbsp;Zhencang Zheng ,&nbsp;Shenglu Jiang ,&nbsp;Lingling Zhang ,&nbsp;Xiufeng Tang","doi":"10.1016/j.neo.2025.101260","DOIUrl":"10.1016/j.neo.2025.101260","url":null,"abstract":"<div><h3>Background</h3><div>Intratumoral heterogeneity contributes to therapy resistance and immune evasion in breast cancer, making treatment strategies more complex. This study integrates single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq deconvolution to characterize tumor subpopulations and develop a robust prognostic model.</div></div><div><h3>Methods</h3><div>We employed a multi-omics approach combining scRNA-seq, spatial transcriptomics, and bulk RNA-seq data deconvolution to explore the molecular diversity within breast cancer tumors. Tumor subtypes were identified based on distinct gene expression profiles, and functional pathway analysis was conducted to evaluate associations with clinical outcomes, including therapy resistance and immune evasion. Data from TCGA and GEO cohorts were integrated to validate the prognostic and immune-related findings. A CoxBoost+GBM algorithm was used to develop a robust prognostic model for patient survival and immunotherapy response prediction.</div></div><div><h3>Results</h3><div>Five distinct tumor subtypes were identified, each with unique functional profiles, underscoring the complexity of breast cancer heterogeneity. Basal-like breast cancer (BLBC) cells were found to play a central role in immune evasion and poor immunotherapy response, with high basal-like cell infiltration correlating with worse survival outcomes. Spatial transcriptomics revealed the widespread presence of BLBC cells across clinical subtypes, including ER+ tumors, suggesting their involvement in therapy resistance. A prognostic model based on CoxBoost+GBM demonstrated strong predictive power for patient survival and immunotherapy efficacy.</div></div><div><h3>Conclusions</h3><div>This study provides a comprehensive view of the genetic and immune determinants of breast cancer heterogeneity, with a focus on BLBC’s role in immune escape and treatment resistance. These insights enhance the potential of multi-omics approaches in precision prevention, early detection, and personalized immunotherapy strategies.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101260"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “P53-independent partial restoration of the p53 pathway in tumors with mutated p53 through ATF4 transcriptional modulation by ERK1/2 and CDK9” [Neoplasia, volume 23 (2021) 304325]","authors":"Xiaobing Tian ,&nbsp;Nagib Ahsan ,&nbsp;Amriti Lulla ,&nbsp;Avital Lev ,&nbsp;Philip Abbosh ,&nbsp;David T. Dicker ,&nbsp;Shengliang Zhang ,&nbsp;Wafik S. El-Deiry","doi":"10.1016/j.neo.2025.101249","DOIUrl":"10.1016/j.neo.2025.101249","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101249"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNβ−pSTAT1-IRF1 axis controls colorectal tumor development through induction of immunogenic Ly6C+myeloid cells","authors":"Yan Li ,&nbsp;Yanmin Wu ,&nbsp;Liyan Liang ,&nbsp;Xufeng Yao ,&nbsp;Yiyang Pan ,&nbsp;Lurong Zhang ,&nbsp;Yaxin Wang ,&nbsp;Jian Zhang ,&nbsp;Kwan T Chow ,&nbsp;Chunwan Lu","doi":"10.1016/j.neo.2025.101261","DOIUrl":"10.1016/j.neo.2025.101261","url":null,"abstract":"<div><div>It has been extensively studied that IFN-I inhibits tumor progression through their intrinsic functions in tumor cells, of which, regulating tumor cell immunogenicity is a critical way. Besides to tumor cells, myeloid cells also comprise a major component of tumor microenvironment. Nevertheless, whether IFN-I modulates the immunogenicity and function of myeloid cells in tumor microenvironment is less explored. In this research, we report that IFNβ effectively induces Ly6C⁺ myeloid cell differentiation in vitro in mouse. In human PBMCs, CD14⁺CD33⁺ monocytic population was consistently accumulated in the presence of IFNβ. In agreement, overexpression of IFNβ in tumor microenvironment by IFNBCOL01 treatment resulted in dramatic increase of tumor-infiltrating Ly6C⁺ myeloid cells and obvious tumor growth control in vivo. Of note, overexpression of IFNβ promotes the immunogenic Ly6C⁺CD103⁺CD11c⁺ subset accumulation in tumor-infiltrating myeloid cells. At the molecular level, we illustrated that the pSTAT1 directly binds to the <em>irf1</em> promoter and that IRF1 directly binds to the <em>Ly6C</em> promoter in myeloid cells both in vitro and in vivo. Furthermore, anti-Ly6C blockade therapy significantly reversed the anti-tumor effect of IFNBCOL01 by restoring NOS2 expression and consequently suppressing T cell functions in tumor-bearing mice. Overall, our findings determine that IFNβ drives myeloid cells to differentiate into Ly6C⁺ subset via the stimulation of pSTAT1-IRF1 axis in myeloid cells. In addition, IFNβ inhibits the immunosuppressive enzyme NOS2 expression in Ly6C⁺ myeloid cells, which may decrease the potential immunosuppressive function of NOS2 to boost the T cell function to repress tumor, thus proposing a new perspective for the anti-tumor mechanism of IFN-I.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101261"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “6-Aminonicotinamide, a G6PD inhibitor, mitigates CAPS1 reduction mediated HCC metastasis via ERK and GSK3β signals” [Neoplasia volume 70 (2025) 101239]","authors":"Xiahui Lin ,&nbsp;Yingying Xu ,&nbsp;Encheng Bai ,&nbsp;Yiran Deng ,&nbsp;Wei Zhang ,&nbsp;Ruyi Xue ,&nbsp;Si Zhang ,&nbsp;Li Zhang ,&nbsp;Wenqing Tang ,&nbsp;Ling Dong ,&nbsp;She Chen","doi":"10.1016/j.neo.2025.101247","DOIUrl":"10.1016/j.neo.2025.101247","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101247"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynasore as a dual modulator of lipid rafts and cell death in pancreatic cancer","authors":"Jakob S. Hamilton ,&nbsp;Rekha R. Garg ,&nbsp;Ryan M. Thomas","doi":"10.1016/j.neo.2025.101254","DOIUrl":"10.1016/j.neo.2025.101254","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States and predicted to soon surpass colorectal cancer as the second. The lack of screening tests, advanced stage at diagnosis, and resistance to current treatment regimens underscore the urgent need for novel therapeutic strategies. Targeting lipid rafts, which are specialized membrane microdomains integral to cancer-related processes such as the epithelial-mesenchymal transition, angiogenesis, and metastatic dissemination, offers a promising strategy to combat this deadly disease. As these catalytic platforms regulate signal transduction pathways key to both cell survival and chemoresistance, we investigated the effects of their disruption on PDAC programmed cell death and proliferation using the dynamin inhibitor, Dynasore. In a panel of human PDAC cell lines, Dynasore reduced lipid rafts in the plasma membrane, resulting in increased oxidative and proteotoxic stress which activated the ATR-Chk1 DNA damage response and initiated programmed cell death. Caspase-1 activation led to pyroptosis in the human PDAC cell lines, BxPC-3 and MIA PaCa-2, while Caspase-3 activation induced apoptosis in MIA PaCa-2 and L3.6pl. These cell-specific cell death responses resulted in dose- and time-dependent antiproliferative effects that enhanced gemcitabine cytotoxicity. Our findings suggest that lipid raft inhibition can modulate proliferation, distinct cell death pathways, and treatment response in PDAC. Given the limitations of current therapies, these results emphasize the need for further investigation into lipid raft-targeting agents in combination with chemotherapy to overcome chemoresistance in pancreatic cancer.</div></div><div><h3>Significance</h3><div>Dynasore exerts potent anti-proliferative and synergistic effects with gemcitabine i<em>n vitro</em> by disrupting lipid rafts and differentially inducing programmed cell death, highlighting its potential as a novel therapy in PDAC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101254"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral AZD5438 is a clinically translatable otoprotectant against cisplatin-induced hearing loss","authors":"Yunlong Huang ,&nbsp;Xintian Zhang ,&nbsp;Enrick Vesanes ,&nbsp;Tal Teitz ,&nbsp;Jian Zuo","doi":"10.1016/j.neo.2025.101250","DOIUrl":"10.1016/j.neo.2025.101250","url":null,"abstract":"<div><div>Cisplatin-based chemotherapy causes hearing loss in 40–60 % of all patients, yet effective preventative options remain limited. Building on prior animal studies, we demonstrate that oral administration of AZD5438, a potent and selective CDK2 inhibitor, provides dose-dependent protection against hearing loss in a clinically relevant multi-dose cisplatin mouse model. Protective doses (4.7 and 9.4 mg/kg b.i.d.) fall within the human-equivalent maximum tolerated dose range established in AstraZeneca trials, and exhibit plasma pharmacokinetics comparable to those in humans. Importantly, AZD5438 at 9.4 mg/kg b.i.d. does not reduce cisplatin’s anti-tumor efficacy in a testicular cancer xenograft model, consistent with <em>in vitro</em> findings. These results support AZD5438 as a promising candidate for clinical trials to prevent cisplatin-induced hearing loss while preserving cancer treatment efficacy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101250"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the antitumor efficacy using a combination of FGFR4 Inhibitor (H3B-6527) and oxaliplatin in gastric cancer","authors":"Nadeem Bhat ,&nbsp;Mohammed Soutto ,&nbsp;Zheng Chen ,&nbsp;Marwah Al-Mathkour ,&nbsp;Silvia Giordano ,&nbsp;Mohammed Chwihne ,&nbsp;Melanie Genoula ,&nbsp;Farah Ballout ,&nbsp;Shoumin Zhu ,&nbsp;Oliver G McDonald ,&nbsp;Wael El-Rifai","doi":"10.1016/j.neo.2025.101257","DOIUrl":"10.1016/j.neo.2025.101257","url":null,"abstract":"<div><div>Oxaliplatin, a platinum-based anticancer drug, is commonly used to treat gastrointestinal cancers, including gastric cancer. However, resistance to platinum-based therapies often leads to poor clinical outcomes for gastric cancer patients. Overexpression and activation of FGFR4 signaling have been identified as drivers of tumorigenesis in several types of cancer, including gastric cancer. In this study, we investigated the therapeutic efficacy of combining the FGFR4 inhibitor H3B-6527 with oxaliplatin using in vitro and in vivo gastric cancer models. Using gastric cancer cell lines, cell viability and clonogenic cell survival assays revealed that the combination treatment significantly reduced cancer cell viability and colony formation, compared to either agent alone (<em>p</em> &lt; 0.01). Interestingly, treatment with oxaliplatin alone increased FGFR4 expression in the resistant cancer cell population. Western blot analysis confirmed the heightened DNA damage (γH2AX, cleaved PARP) alongside suppressed pro-survival signals (phospho-STAT3 and BCL2 family). Apoptosis was markedly enhanced, as demonstrated by Caspase-3/7 and TUNEL assays (<em>p</em> &lt; 0.01). In human gastric cancer-derived tumoroids, the combination therapy significantly reduced both the size and number of tumoroids. In patient-derived xenograft (PDX) models, the combined treatment approach outperformed single-agent treatments in reducing tumor growth and improving survival. Immunofluorescence and immunohistochemistry analyses of PDX tumors showed an increase in DNA damage (γH2AX) and apoptosis (cleaved caspase-3) along with a reduction in cell proliferation (KI67).</div><div>These findings indicate that H3B-6527 enhances gastric cancer sensitivity to oxaliplatin by amplifying DNA damage and disrupting cell survival pathways. This study provides a rationale for clinical trials targeting FGFR4 in gastric cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101257"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUD4-ZMYND8-DDX3X Axis Drives Immunosuppressive Microenvironment in Spinal Metastases of Triple-Negative Breast Cancer","authors":"Bing Liang ,&nbsp;Annan Hu ,&nbsp;Hongwei Lu ,&nbsp;Hao Zhou ,&nbsp;Qing Chen ,&nbsp;Chao Jia ,&nbsp;Jinjin Wang ,&nbsp;Libo Jiang ,&nbsp;Wei Hong ,&nbsp;Jian Zhou ,&nbsp;Jian Dong","doi":"10.1016/j.neo.2025.101259","DOIUrl":"10.1016/j.neo.2025.101259","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) exhibits a high propensity for spinal metastasis, leading to severe morbidity and limited therapeutic responses. However, the molecular mechanisms driving spinal colonization remain poorly defined. Here, we identify the epigenetic reader ZMYND8 as a key mediator of TNBC spinal metastasis. ZMYND8 is significantly upregulated in spinal metastatic lesions and correlates with adverse patient outcomes. Transcriptomic profiling reveals that spinal metastases display profoundly immunosuppressive microenvironments, with elevated M2 macrophage infiltration positively associated with ZMYND8 expression. Mechanistically, ZMYND8 functions as a scaffold protein that promotes assembly of the DDX3X–CK1ε complex, thereby activating WNT/β-catenin signaling and promoting spinal metastasis. Furthermore, we identify OTUD4 as a bona fide deubiquitinase that directly interacts with and stabilizes ZMYND8, thereby enhancing TNBC cell migration, invasion, and spinal colonization. The resulting OTUD4–ZMYND8–DDX3X signaling axis drives canonical WNT/β-catenin signaling, upregulates CSF1 expression and promotes M2 polarization of macrophages, collectively fostering invasive behavior and establishing an immunosuppressive niche conducive to spinal metastasis. Collectively, these findings establish the OTUD4–ZMYND8–DDX3X axis as a pivotal regulator of spinal metastasis in TNBC and highlight its potential as a therapeutic target for inhibiting metastatic progression.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"71 ","pages":"Article 101259"},"PeriodicalIF":7.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}