Molecular Cancer Research最新文献

{"title":"Interaction of NDRG1 and TGM2 Modulates DNA Replication and Repair.","authors":"Hanna M Doh, Nina Kozlova, Kayla A Cruz, Taru Muranen","doi":"10.1158/1541-7786.MCR-25-0743","DOIUrl":"10.1158/1541-7786.MCR-25-0743","url":null,"abstract":"<p><p>In tumor cells, DNA replication is constantly challenged by endogenous and exogenous sources, referred to as replication stress, and various pathways have evolved to mitigate this stress in cancer. We recently identified an extracellular matrix (ECM)-induced DNA repair pathway involving N-myc downstream regulated gene 1 (NDRG1). Matrix-induced signaling results in NDRG1-dependent protection from chemotherapy-induced replication stress. To uncover further mechanistic details of NDRG1-mediated effects on DNA replication, we identified transglutaminase 2 (TGM2) as a novel NDRG1-binding partner. TGM2 is an acyltransferase that catalyzes Ca(2+)-dependent protein modifications. This interaction was enriched upon chemotherapy-induced replication stress and also upon ECM-induced signaling. Our data show that TGM2 depletion significantly slows replication fork progression, and this phenotype is dependent on TGM2 catalytic activity and its nuclear localization. Our study further identifies a putative NDRG1-TGM2 binding site and shows that the physical interaction between NDRG1 and TGM2 is required for efficient DNA replication.</p><p><strong>Implications: </strong>This study reveals a previously unrecognized nuclear function for NDRG1 and TGM2 in regulating DNA replication fork stability and recovery, and uncovers a stress-responsive mechanism that supports replication homeostasis in cancer cells and advances our understanding of how extracellular signals are integrated with replication and repair pathways.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"601-617"},"PeriodicalIF":5.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SF3B4-QKI Splicing Complex Generates Circ-FNDC3B and Mediates Breast Cancer Inhibition.","authors":"Liu Sen, Liu Haiting, Cui Xiujie, Guo Xiangyu, Chen Shiming, Ma Ranran, Aiyan Xing, Liu Tiantian, Wang Yawen, Peng Gao","doi":"10.1158/1541-7786.MCR-25-0880","DOIUrl":"10.1158/1541-7786.MCR-25-0880","url":null,"abstract":"<p><p>Circular RNA (circRNA), usually produced through a back-splicing process, is a type of single-stranded RNA that is covalently bonded. Our research indicated that a spliceosome composed of SF3B4 and QKI promoted the back-splicing of FNDC3B, thereby promoting the generation of circRNA FNDC3B (Circ-FNDC3B). Circ-FNDC3B is underexpressed in breast cancer and is characterized by a high metastatic risk. In addition, Circ-FNDC3B expression was reduced in breast cancer with larger tumor diameter, later clinical staging, and lymph node metastasis. The secondary structure of Circ-FNDC3B, specifically the 356 to 425 bp sequence, interacts with the biotin carboxylase domain of pyruvate carboxylase (PC), inhibiting the activity of PC. Low expression of Circ-FNDC3B enhances the activity of PC, thereby facilitating cell proliferation. The underlying mechanism involves the promotion of aspartate synthesis and the acceleration of the citrate-pyruvate cycle. This, in turn, promotes NADPH synthesis, thus alleviating the oxidative damage induced by reactive oxygen species. Furthermore, in human breast cancer organoids and a mouse model of lung metastasis, we have validated that exogenous expression of Circ-FNDC3B can inhibit the activity of PC, thereby suppressing tumor proliferation and promoting tumor cell apoptosis. In general, upregulating the expression of Circ-FNDC3B can impede the progression of breast cancer.</p><p><strong>Implications: </strong>This study reveals significant heterogeneity in the expression of circRNAs commonly used to identify breast cancer metastasis and confirms that circRNAs affect the metabolic state of breast cancer through their binding proteins.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"576-588"},"PeriodicalIF":5.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468977","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":"ID4 Suppresses Proliferation and Macrophage Polarization in Esophageal Carcinoma through Interaction with TCF4.","authors":"Tianci Han, Junwei Xie, Wei Tong, Liang Zhang","doi":"10.1158/1541-7786.MCR-25-0686","DOIUrl":"10.1158/1541-7786.MCR-25-0686","url":null,"abstract":"<p><p>The poor prognosis of esophageal carcinoma highlights the need to identify novel targets for esophageal carcinoma treatment. We found that the inhibitor of differentiation 4 (ID4) was decreased in esophageal carcinoma tumor tissues, and its expression was associated with the survival of patients with esophageal carcinoma. However, the role of ID4 in esophageal carcinoma remains unclear. In this study, we found that overexpression of ID4 suppressed the cell proliferation of esophageal carcinoma in vitro, as well as tumor growth in vivo, whereas knockdown of ID4 presented the opposite trend. On the other hand, esophageal carcinoma cells with the overexpression of ID4 reduced macrophage migration and M2 polarization. However, significant increases in macrophage migration and M2 polarization were observed in cultures with ID4 silenced. Interestingly, C-C motif ligand 2 (CCL2) was found to mediate the function of ID4 in macrophage polarization. Mechanistically, we identified for the first time that ID4 interacted physically with transcription factor 4 (TCF4) to inactivate TCF4 transcriptional activity, which led to a decrease in CCL2 expression. Moreover, the RNA-binding protein cell cycle-associated protein 1 bound to ID4 mRNA and downregulated its stability, which may contribute to its low expression in esophageal carcinoma. Taken together, these results support a novel hypothesis that ID4 downregulation may contribute to the development of esophageal carcinoma by interacting with TCF4, resulting in abnormal proliferation of esophageal carcinoma cells and tumor-associated macrophage infiltration. ID4 may contribute to the innovation of esophageal carcinoma biotherapy.</p><p><strong>Implications: </strong>ID4 inhibits esophageal carcinoma by suppressing cancer cell proliferation and macrophage M2 polarization, and ID4 could be a potential prognostic marker for patients with esophageal carcinoma.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"458-472"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326745","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":"The Trifecta of Polo-Like Kinases, Cancer, and the Immune System: Emerging Intersections and Therapeutic Insights.","authors":"Tanya Jaiswal, Carl A Shirley, Ichwaku Rastogi, Gagan Chhabra, Hao Chang, Nihal Ahmad","doi":"10.1158/1541-7786.MCR-25-1138","DOIUrl":"10.1158/1541-7786.MCR-25-1138","url":null,"abstract":"<p><p>Cancer remains one of the most pressing global health challenges, with immunotherapy being a promising treatment option. However, numerous clinical challenges, such as recurrence and resistance, persist, underscoring the urgent need for a deeper understanding of the mechanisms that influence immune responses in cancer. Polo-like kinases (PLK), a family of enzymes with five members, PLK1 through PLK5, have been implicated in cancer progression, and their inhibition is being actively explored for cancer management. Although past studies of the PLK family are largely confined to their role in the cell cycle and corresponding chromatin dynamics, recent research has unveiled important connections between PLKs and cancer immunity, particularly in relation to critical signaling pathways such as interferon (IFN) signaling, immunogenic cell death, transforming growth factor beta (TGFβ) signaling, and FAS/FASL signaling. Although much of the research has focused on PLK1, additional members of the PLK family are beginning to attract attention due to their potential implications in cancer immunity. Understanding the intricate role of PLKs in cancer immunity is an emerging field with tremendous potential. This review offers a comprehensive overview of current knowledge connecting the members of the PLK family with cancer immunology and provides considerations for further research to uncover how PLK signaling can be strategically targeted to optimize cancer immunotherapy and enhance clinical responses.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"444-457"},"PeriodicalIF":5.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting the Cell Cycle to Lipid Metabolism in Cancer: Their Reciprocal Roles and Opportunity for Therapeutic Exploitation.","authors":"Joshua T Hodgson, Lisa M Butler, Margaret M Centenera","doi":"10.1158/1541-7786.MCR-25-1270","DOIUrl":"10.1158/1541-7786.MCR-25-1270","url":null,"abstract":"<p><p>Uncontrolled cellular proliferation is a hallmark of cancer that is both driven by deregulation of the cell cycle and fueled by metabolic reprogramming. Among the metabolic alterations detected, lipid metabolism is markedly upregulated to provide resources for proliferating cancer cells. Each cell cycle requires lipids for membrane synthesis, energy production, and cellular signaling, yet the mechanistic relationship linking the cell cycle to lipid metabolism in cancer remains incompletely understood. Recent advances in lipidomic technologies that enable comprehensive profiling of the cancer lipidome have provided new insights into the interconnections between these two pathways. This review describes how cell-cycle regulators influence various aspects of lipid metabolism in models of cancer and the effect of cell-cycle perturbation on cellular lipid profiles. We further describe lipid metabolic changes associated with response and resistance to cell-cycle inhibitors in cancer and offer insight into how these findings may inform the development of clinical biomarkers and new therapeutic strategies.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"411-421"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344782","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":"Epigenetic Atlas of Bladder Cancer Reveals Master Transcription Factors and Risk-Associated Regulatory Elements in Luminal and Basal-Squamous Molecular Subtypes.","authors":"Elio Adib, Amin H Nassar, Sarah Abou Alaiwi, Sylvan C Baca, Timothy Hanlon, Elias Bou Farhat, Yan Tang, Rosario I Corona, Ji-Heui Seo, Talal El Zarif, Marcos A S Fonseca, Andres M Acosta, Magdalena Losko, Ziwei Zhang, Michelle S Hirsch, Alexander Gusev, Kate Lawrenson, Kent W Mouw, Toni K Choueiri, David J Kwiatkowski, Matthew L Freedman","doi":"10.1158/1541-7786.MCR-25-1385","DOIUrl":"10.1158/1541-7786.MCR-25-1385","url":null,"abstract":"<p><p>We generated 64 epigenomic datasets using chromatin immunoprecipitation with sequencing and assay for transposase-accessible chromatin sequencing profiling on 28 fresh bladder cancer specimens of luminal and basal-squamous expression subtypes. An integrated analysis of core regulatory circuitry, enhancer activity, and transcription factor (TF) expression specificity nominated 23 luminal-specific and 14 basal-squamous-specific candidate master TFs (MTF), including established regulators like FOXA1, PPARG, and GATA3 for luminal bladder cancer and TP63 for basal-squamous bladder cancer, as well as new basal-squamous MTF candidates, SNAI2 and CEBPB. GRHL2, a regulator of subtype differentiation, was identified as a common MTF to luminal and basal-squamous bladder cancers. Cis-regulatory elements were enriched up to 80-fold for bladder cancer risk variants. Keratinization pathways were enriched in genetically determined basal-squamous sites, whereas carcinogen glucuronidation pathways were enriched in luminal sites. Integrating germline variation and epigenomics through a cistrome-wide association study identified a new bladder cancer risk locus upstream of SPINK1 and linked 10 of 19 bladder cancer risk loci to regulatory elements from a 350,000-sample genome-wide association study.</p><p><strong>Implications: </strong>Overall, this integrative computational analysis provides comprehensive insights into the epigenomic underpinnings of bladder cancer subtypes, nominates candidate master regulators of cellular identity for future experimental validation, and reveals how regulatory elements harboring inherited germline variation may contribute to bladder cancer risk and biology.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"504-517"},"PeriodicalIF":5.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Biology of the Blood-Brain Tumor Barrier in Brain Cancer.","authors":"Jorge L Jimenez Macias, Philippa Vaughn-Beaucaire, Jingxu Yan, Jasmine Clark, Sean E Lawler","doi":"10.1158/1541-7786.MCR-25-0908","DOIUrl":"10.1158/1541-7786.MCR-25-0908","url":null,"abstract":"<p><p>Brain cancers are among the most lethal and challenging malignancies to treat in the clinic. An important impediment to effectively treat brain tumors is the blood-brain tumor barrier (BTB), an interface generated between the blood-brain barrier and intracranial tumors, creating a tumor-permissive perivascular microenvironment. The BTB loses endothelial barrier properties in a heterogeneous manner across the tumor but continues to impede effective intratumoral drug delivery, dramatically decreasing the potential of many antineoplastic pharmaceutics. This review will provide a summary of our current understanding of the molecular composition and cellular architecture of the BTB, focusing on glioblastoma and other high-grade gliomas. We will summarize different multiomic and spatial studies performed with the goal to reveal unknown traits of the brain cancer-associated vasculature and identify molecular targets of therapeutic relevance. Our work aims to consolidate our current understanding of the vasculature in brain tumors and the insights held regarding its role in brain cancer biology and therapeutic drug delivery.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"422-433"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487031","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":"ARID1A Deficiency in Diffuse-Type Gastric Cancer Promotes a Pyrimidine Metabolic Vulnerability.","authors":"Harumi Hirano, Hideki Makinoshima, Hideaki Ogiwara","doi":"10.1158/1541-7786.MCR-25-1069","DOIUrl":"10.1158/1541-7786.MCR-25-1069","url":null,"abstract":"<p><p>Loss-of-function mutations in ARID1A define an aggressive subtype of diffuse gastric cancer (DGC) that is often resistant to standard chemotherapy. In this study, we uncover a precise metabolic vulnerability in ARID1A-deficient DGC driven by a specific transporter defect. Through integrated metabolomic and transcriptomic analyses, we demonstrate that ARID1A loss transcriptionally represses the high-affinity nucleoside transporter SLC28A3. Our profiling revealed a critical lack of redundancy in the concentrative transporter family in DGC, establishing a strict reliance on SLC28A3 for maintaining intracellular deoxycytidine (dC) pools. Consequently, ARID1A deficiency creates a severe \"low-dCTP\" metabolic bottleneck. We show that the dC analogue gemcitabine exploits this state through a distinct functional dichotomy: it enters via intact equilibrative transporters to target cells that have lost their competitive dC barrier. Mechanistically, gemcitabine exerts a \"dual- hit\" effect by outcompeting the scarce dC pool for DNA incorporation while simultaneously inhibiting ribonucleotide reductase, thereby blocking de novo nucleotide synthesis. This synergistic collapse of pyrimidine metabolism was validated in patient-derived ex vivo cultures and in vivo peritoneal dissemination models. Our findings provide a robust mechanistic basis for repurposing gemcitabine as a precision therapy for ARID1A-deficient DGC, offering a potent strategy for this intractable malignancy.</p><p><strong>Implications: </strong>This work uncovers a metabolic vulnerability in ARID1A-deficient gastric cancer caused by SLC28A3 loss. It provides a compelling rationale for repurposing gemcitabine as a targeted therapy for this intractable malignancy.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"518-532"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308313","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":"LINE-1 Activation in Endocrine-Related Cancers: Molecular Mechanisms and Translational Implications.","authors":"Bruna Sousa Pessoa, Nathália Da Roz D'Alessandre, Gabriela Der Agopian Guardia, Juliana Moreira Marques, Christiane Gruetzmacher, Flora Ladeira Craveiro, Paula Fontes Asprino, Pedro Alexandre Favoretto Galante, Rafael Loch Batista","doi":"10.1158/1541-7786.MCR-25-0682","DOIUrl":"10.1158/1541-7786.MCR-25-0682","url":null,"abstract":"<p><p>Long interspersed nuclear element (LINE-1) retrotransposons are increasingly recognized as active molecular players in tumorigenesis, particularly through mechanisms involving genomic instability, epigenetic deregulation, and disruption of transcriptional networks. However, their specific role in endocrine-related cancers remains underexplored despite accumulating evidence of widespread LINE-1 derepression in tumors of the thyroid, adrenal, pituitary, and prostate glands. In this review, we provide a focused synthesis of the mechanistic consequences of LINE-1 reactivation in endocrine tumors. We discuss how hypomethylation of LINE-1 loci and overexpression of retrotransposon-encoded proteins [open reading frame 1 (ORF1p) and open reading frame 2 proteins] may contribute to DNA damage, copy-number alterations, and impaired p53 signaling. We also explore emerging evidence that ORF1p may act as a co-regulator of nuclear hormone receptors, thereby linking retroelement biology with hormone-dependent tumor behavior. Beyond these molecular insights, we highlight translational opportunities rooted in LINE-1 biology, including the use of ORF1p as a surrogate biomarker of epigenetic instability, and therapeutic strategies targeting the retrotransposon life cycle. By bridging foundational mechanisms with endocrine-specific tumor phenotypes, this review positions LINE-1 derepression as a unifying framework with both biological and clinical relevance in endocrine-related cancers.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"434-443"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284535","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":"UBE2B Drives NF-κB Signaling and Gastric Cancer Progression through BIRC2-Mediated K63-Linked Ubiquitination of TRAF1.","authors":"Jiancheng He, Xinkun Huang, Danjie Xing, Shun Chen, Yu Chen, Wanjiang Xue, Yilin Hu","doi":"10.1158/1541-7786.MCR-25-0884","DOIUrl":"10.1158/1541-7786.MCR-25-0884","url":null,"abstract":"<p><p>Ubiquitin (Ub)-conjugating enzymes (E2 enzyme) are essential mediators of Ub-dependent signaling cascades, governing diverse cellular processes such as proteolysis and transcriptional regulation. Despite increasing evidence linking E2 enzymes to tumorigenesis, their precise roles in gastric cancer remain incompletely defined. In this study, we identified UBE2B as a key oncogenic E2 enzyme significantly upregulated in gastric cancer tissues through integrative bioinformatics analysis and clinical validation. High UBE2B expression was associated with poor patient prognosis and aggressive clinicopathologic features. Functional assays demonstrated that UBE2B promotes gastric cancer cell proliferation both in vitro and in vivo. Mechanistically, UBE2B interacts with the E3 ligase baculoviral IAP repeat-containing 2 (BIRC2) to catalyze K63-linked ubiquitination of TNF receptor-associated factor 1 (TRAF1), thereby amplifying NF-κB signaling. Furthermore, chromatin immunoprecipitation and luciferase reporter assays revealed that the NF-κB subunit P65 directly binds to the UBE2B promoter, enhancing its transcription and forming a feedforward regulatory loop. This UBE2B-BIRC2-TRAF1 axis, coupled with the UBE2B-TRAF1-P65 feedback circuitry, establishes a self-sustaining mechanism that drives NF-κB hyperactivation and tumor cell proliferation. Collectively, our findings highlight UBE2B as a critical modulator of gastric cancer progression and a potential target for therapeutic intervention.</p><p><strong>Implications: </strong>This study characterizes the UBE2B-BIRC2-TRAF1 axis as a driver of NF-κB hyperactivation, identifying UBE2B as a prognostic biomarker and a potential therapeutic target for disrupting this oncogenic feedback loop in gastric cancer.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"487-503"},"PeriodicalIF":4.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143072","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}