Journal of Cancer最新文献

{"title":"Subtype-Dependent Transcriptional Coupling Between DNMT1 and E2F-Linked Proliferative Programs in Breast Cancer: A Dual-Cohort Transcriptomic Analysis.","authors":"Ping Xiao, Yiqun Xie, Ruijie Niu, Ming Shan, Zhiwu Dong, Yang Shi","doi":"10.7150/jca.134046","DOIUrl":"10.7150/jca.134046","url":null,"abstract":"<p><strong>Background: </strong>DNMT1 is a maintenance DNA methyltransferase involved in replication-coupled epigenetic regulation and is frequently expressed in highly proliferative tumors. Although DNMT1 has been linked to RB-E2F-related transcriptional programs, the reproducibility and subtype dependence of this association in breast cancer remain incompletely defined.</p><p><strong>Methods: </strong>We performed a dual-cohort integrative transcriptomic analysis using TCGA-BRCA as the discovery cohort and METABRIC as the external validation cohort. DNMT1 expression was evaluated across tumor status and subtype annotations, with PAM50 used for all core multivariable and interaction analyses and METABRIC CLAUDIN_SUBTYPE used only for descriptive stratification. DNMT1-associated transcriptional programs were characterized in TCGA-BRCA using differential expression analysis and pathway enrichment. E2F-related transcriptional activity was summarized using an E2F metagene score derived from 122 available genes in the MSigDB Hallmark E2F Targets gene set. Cross-cohort Spearman correlation analyses, multivariable linear models, MKI67-adjusted sensitivity analyses, and likelihood-ratio tests for E2F2 × PAM50 interaction were performed.</p><p><strong>Results: </strong>DNMT1 expression was elevated in breast tumors and was highest in basal-like tumors. In TCGA-BRCA, high DNMT1 expression was associated with proliferation- and replication-related transcriptional programs, including cell-cycle progression, DNA replication, homologous recombination, and replication stress-related pathways. Across TCGA-BRCA and METABRIC, DNMT1 expression was positively associated with the E2F metagene score, E2F2, E2F3, and MKI67. In multivariable models adjusted for PAM50 subtype and age, the E2F metagene score remained associated with DNMT1 expression in both TCGA-BRCA (standardized β = 0.889, 95% CI 0.837-0.941) and METABRIC (β = 0.578, 95% CI 0.517-0.638). In joint E2F2/E2F3 models, cross-cohort evidence was strongest for E2F2, whereas the E2F3 association was more cohort-dependent and was attenuated in METABRIC. MKI67 adjustment attenuated but did not abolish the E2F2 association in both cohorts. Formal interaction testing supported subtype-dependent heterogeneity in the E2F2-DNMT1 association in both TCGA-BRCA and METABRIC.</p><p><strong>Conclusions: </strong>DNMT1 shows reproducible, subtype-dependent transcriptional coupling with E2F-linked proliferative programs in breast cancer, with the most consistent cross-cohort evidence observed for the E2F metagene score and E2F2. These findings should be interpreted as hypothesis-generating transcriptomic associations rather than evidence of direct mechanistic causality.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 9","pages":"1547-1557"},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative coagulation profiling and postoperative lower-extremity venous thrombosis risk prediction in glioma patients.","authors":"Ping Pu, Miao Yang, Hong Zhou, Yan Xiang, Shuai Wang, Shengqing Lv, Wei Yang","doi":"10.7150/jca.136435","DOIUrl":"10.7150/jca.136435","url":null,"abstract":"<p><strong>Background: </strong>Lower-extremity venous thrombosis (LEVT) is highly prevalent among glioblastoma patients, creating a therapeutic dilemma in clinical management.</p><p><strong>Methods: </strong>We retrospectively analyzed preoperative coagulation parameters in primary glioma, trigeminal neuralgia, and meningioma patients. Glioma cohorts were stratified by IDH1 and LEVT status, with coagulation factor expression analyzed using public databases. Perioperative coagulation dynamics were evaluated, and an LEVT prediction model was constructed.</p><p><strong>Results: </strong>Glioma patients exhibited a hypercoagulable state compared with non-neoplastic and benign tumor controls, with IDH1-Wt cases showing particularly elevated fibrinogen levels versus IDH1-Mutant gliomas. Perioperative analysis revealed universal decreases in APTT and fibrinogen, while PT prolongation was exclusive to IDH1-Wt cases and APTT shortening predominated in IDH1-Mutant patients. Spatial and single-cell analyses demonstrated IDH1 mutation-specific overexpression patterns of coagulation factors with prognostic significance. LEVT patients were characterized by shorter preoperative APTT, lower postoperative fibrinogen, and distinct coagulation parameter trajectories. These findings informed the development of a high-performance predictive model incorporating perioperative coagulation markers for LEVT risk assessment.</p><p><strong>Conclusion: </strong>We characterized perioperative coagulation profiles in glioma patients and developed an accurate LEVT prediction model, enabling early intervention to improve outcomes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 9","pages":"1558-1569"},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of single nucleotide polymorphism of <i>SYNE1</i> gene in Oral squamous cell carcinoma.","authors":"Ming-Ju Hsieh, Hsin-Yu Ho, Yu-Sheng Lo, Bharath Kumar Velmurugan, Shanmugavadivu Muthusamy, Min-Yun Kao, Chia-Chieh Lin, Yi-Ching Chuang, Mu-Kuan Chen","doi":"10.7150/jca.139098","DOIUrl":"10.7150/jca.139098","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is one of the major causes of cancer-related mortality in Taiwan and is strongly associated with alcohol consumption, betel quid chewing, and cigarette smoking. Spectrin repeat-containing nuclear envelope protein 1 (<i>SYNE1</i>) is downregulated in various cancer types, but its role in OSCC remains unclear. The aim of the present study is to investigate the association between single nucleotide polymorphisms (SNPs) of <i>SYNE1</i> gene (rs2295190, rs2306916, rs2695261, rs9371601) and OSCC susceptibility as well as clinical outcomes in 377 OSCC patients and 480 cancer-free controls. No significant association was found between any of the four SNPs and overall OSCC risk. However, in OSCC patients, <i>SYNE1</i> rs2295190 GT+TT genotype was significantly associated with advanced clinical stage (Stage III/IV) compared to the GG genotype (AOR=2.271, 95% CI: 1.081-4.771, <i>p=0.030</i>). This association was particularly evident in betel nut chewers (OR=2.399, 95% CI: 1.026-5.609, <i>p=0.043</i>) and in those using the areca nut with slaked lime and piper betel leaf (OR=3.482, 95% CI: 1.063-11.408, <i>p=0.039</i>). Although no significant association was observed between the four investigated SNPs and overall OSCC susceptibility, the <i>SYNE1</i> rs2295190 GT+TT genotype was significantly associated with advanced clinical stage in OSCC patients. This association was more evident among individuals with betel nut chewing habits, mostly in OSCC patients who consumed areca nut with slaked lime and piper betel leaf. These findings suggest that <i>SYNE1</i> rs2295190 may be associated with OSCC progression rather than overall disease susceptibility, particularly in the context of betel quid exposure.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 9","pages":"1570-1575"},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Overexpression of Platelet-Derived Growth Factor Receptor Α <i>D842V</i> Mutants Prevents Liver Regeneration and Chemically Induced Hepatocarcinogenesis via Inhibition of MET and EGFR: Erratum.","authors":"Zhao-Qing Du, Jian Dong, Mu-Xing Li, Jian-Fei Zhang, Jian-Bin Bi, Yi-Fan Ren, Li-Na Zhang, Rong-Qian Wu, Satdarshan P S Monga, Yi Lv, Xu-Feng Zhang, Hai-Chen Wang","doi":"10.7150/jca.140353","DOIUrl":"https://doi.org/10.7150/jca.140353","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.44492.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1546"},"PeriodicalIF":3.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation Patterns Define Clinical Heterogeneity in Acute Myeloid Leukemia.","authors":"Zhengrong Xu, Ying Zheng, Yi Zheng, Yanyan Yao, Haili Geng, Xiaofan Li, Shao-Yuan Wang, Lili Pan","doi":"10.7150/jca.135267","DOIUrl":"10.7150/jca.135267","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a molecularly heterogeneous malignancy where next-generation sequencing (NGS) has revolutionized risk stratification and treatment paradigms. However, the interplay between mutation cooperativity, clinical phenotypes, and biochemical markers of organ dysfunction remains poorly characterized. This study investigates how co-mutational patterns influence hematological/biochemical parameters and survival outcomes in AML.</p><p><strong>Methods: </strong>In this single-center retrospective study (2017-2024), 1,416 non-M3 AML patients with NGS-confirmed somatic mutations were analyzed. Clinical parameters included hematologic parameters, biochemical markers, and survival outcomes. Multivariate Cox models, Kaplan-Meier analysis, propensity score matching (1:4), and Cohen's d effect sizes were employed to assess mutation-clinical correlations.</p><p><strong>Results: </strong>A higher mutational burden was associated with older age, elevated platelets, and renal impairment, with <i>DNMT3A</i> mutation identified as an independent factor for renal impairment. Multivariable analysis identified higher mutational burden, age, renal impairment, and high white blood cell counts as independent predictors of inferior survival. We identified novel co-occurring (e.g., <i>KRAS</i> and <i>PTPN11</i>; OR = 3.19; 95% CI, 2.97-3.42) or mutually exclusive (e.g., <i>CEBPA</i>-<i>bZIP</i> and <i>NPM1</i>; OR = 0.03; 95% CI, 0.01-0.17) gene pairs (all adjusted <i>P</i> <0.001). The <i>NPM1</i>/<i>IDH1</i> co-mutation elevated blast percentages in bone marrow and peripheral blood compared to either single mutation alone. Three novel triple-mutations were significantly associated with higher mortality: <i>IDH2</i>: <i>FLT3</i>-<i>ITD</i>: <i>NPM1</i> (HR = 4.68), <i>IDH2</i>: <i>SRSF2</i>: <i>ASXL1</i> (HR = 3.31), and <i>RUNX1</i>: <i>TET2</i>: <i>NRAS</i> (HR = 3.08) (all adjusted <i>P</i> <0.05).</p><p><strong>Conclusions: </strong>These findings support integrating genomic and biochemical profiling for AML management, as co-mutation patterns, particularly those affecting renal function, refine risk stratification and highlight the need for tailored monitoring and organ support.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1531-1545"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucosamine Use and Its Association with Colorectal Cancer and Mortality: A Systematic Review and Meta-Analysis.","authors":"Yiling Yan, Manrong Xu, Ruixin Wang, Shengdi Lu, Yun Shen, Feng Liu","doi":"10.7150/jca.133131","DOIUrl":"10.7150/jca.133131","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and aim: &lt;/strong&gt;This systematic review and meta-analysis aimed to evaluate whether habitual glucosamine use is associated with colorectal cancer risk and survival outcomes in the general population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Following PRISMA 2020 guidance, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to January 10, 2026. Prospective cohort studies comparing glucosamine users with non-users and reporting adjusted effect estimates were eligible. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale. Adjusted hazard ratios or relative risks were pooled using fixed- or random-effects models based on heterogeneity quantified with I².&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 347 records, 18 prospective cohort studies met eligibility criteria; five outcomes (colorectal cancer incidence, colorectal cancer-specific mortality, all-cause mortality, cardiovascular mortality, and overall cancer mortality) were quantitatively synthesized. Glucosamine use was associated with a lower incidence of colorectal cancer across 5 studies (pooled HR 0.87, 95% CI 0.82 to 0.92; I² = 36%). For colorectal cancer-specific mortality, the evidence was limited to only 2 studies with substantial heterogeneity (I² = 81%) and effect estimates in opposite directions, and the pooled estimate showed no clear association (pooled RR 0.99, 95% CI 0.57 to 1.71); this outcome should therefore be regarded as inconclusive. Glucosamine use was also associated with lower all-cause mortality in 4 studies (pooled HR 0.84, 95% CI 0.76 to 0.94; I² = 65%), lower cardiovascular mortality in 4 studies (pooled HR 0.82, 95% CI 0.75 to 0.89; I² = 44%), and a modest reduction in overall cancer mortality in 4 studies (pooled HR 0.94, 95% CI 0.91 to 0.98; I² = 7%). Results were stable in leave-one-out sensitivity analyses. All estimates represent associations derived from observational cohort studies and cannot establish causation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Current cohort evidence indicates that glucosamine use is associated with a modestly lower risk of developing colorectal cancer and with lower mortality from all causes, cardiovascular disease, and cancer overall. The evidence for colorectal cancer-specific mortality was based on only 2 studies with substantial heterogeneity and remains inconclusive. Because all included studies were observational, these findings represent associations rather than evidence of a causal protective effect. Given the modest effect sizes, healthy-user bias and residual confounding are plausible and possibly major explanations for the observed associations, and even a small degree of unmeasured confounding could account for part or all of them. Well-designed studies with improved exposure characterization, and ideally causal designs such as Mendelian randomization, are needed to determine whether these associations ","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1520-1530"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Parameters influence Chemosensitivity in Gastric Cancer Cells.","authors":"Kai-Chun Hong, Yi-Chun Chen, You-Syuan Lou, Chia-Chi Tsai, Xu-Chen Liu, Lei-Ni Liang, Chih-Cheng Cheng, Hsin-Hsien Yu, Bor-Chyuan Su","doi":"10.7150/jca.137748","DOIUrl":"10.7150/jca.137748","url":null,"abstract":"<p><p>Mitochondria play crucial roles in the survival of malignant cells in gastric and other types of cancers, and many cancer treatments act at least in part via mitochondrial effects. Although several measurable mitochondrial parameters have been associated with sensitivity of certain cancer cells to treatments, it remains unclear how these parameters differ among cancer cells according to differentiation level and histological type. It also remains unclear whether and how the effects of chemotherapy on mitochondrial parameters might be associated with sensitivity to treatment. In this study, we compared mitochondrial parameters in a panel of gastric cancer cell lines with different characteristics, including AGS (moderately differentiated), SNU-1 (poorly differentiated), KATO III (signet ring cell carcinoma; SRCC), and NUGC-4 (SRCC). We examined differences in basal mitochondrial parameters between the cell lines and the impacts of chemotherapy on each parameter. Our results showed that each cell line showed a different response pattern to cisplatin and 5-fluorouracil. For example, cisplatin was much more effective than 5-fluorouracil at killing SNU-1 gastric cancer cells, while KATO III cells exhibited minimal responses to both chemotherapies. These patterns of cytotoxicity were closely aligned with mitochondrial membrane potential. The different gastric cancer cell lines also displayed differences in basal mitochondrial parameters, but the basal measurements did not directly correlate with sensitivity to chemotherapy. Nevertheless, sensitivity was associated with an integrated profile of basal levels and effects of chemotherapy on mitochondrial parameters. Thus, our study highlights the association between mitochondrial parameters and chemosensitivity among gastric cancer cells with diverse characteristics. These findings may guide the development of more precise treatment strategies and targeted therapies for distinct types of gastric cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1480-1490"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction as a Targetable Vulnerability in Gastric Cancer: From Carcinogenesis to Apoptosis (A Narrative Review).","authors":"Hsi-Lung Hsieh, Ming-Chin Yu, Hui-Ching Tseng, Yi-Hsuan Wu, Tzu-Hao Huang, Ming-Ming Tsai","doi":"10.7150/jca.131081","DOIUrl":"10.7150/jca.131081","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major global health burden and is associated with high mortality worldwide. Current treatment integrates surgery, perioperative or systemic chemotherapy, molecularly targeted therapy, and immune checkpoint blockade; however, efficacy is frequently limited by intratumoral heterogeneity, metabolic plasticity, and therapeutic resistance. Mitochondria, as central regulators of cellular bioenergetics, redox homeostasis, and apoptotic signaling, are profoundly altered in GC. Tumor cells frequently exhibit enhanced aerobic glycolysis accompanied by suppressed oxidative phosphorylation, reflecting mitochondrial metabolic remodeling. Accumulating evidence indicates that mitochondrial dysfunction actively contributes to tumor initiation, progression, and therapeutic resistance in GC. Importantly, these mitochondrial alterations also create metabolic vulnerabilities that may be therapeutically exploitable. Both conventional chemotherapeutic agents and herbal-derived natural compounds have been reported to induce mitochondrial stress responses, including excessive reactive oxygen species (ROS) accumulation, mitochondrial membrane potential loss, and activation of mitochondria-dependent intrinsic apoptotic pathways. In this narrative review, we summarize the major molecular mechanisms underlying mitochondrial dysfunction in GC, highlight mitochondrial-associated prognostic biomarkers, and discuss emerging therapeutic strategies targeting mitochondrial pathways. Collectively, these insights emphasize mitochondrial dysfunction as a candidate therapeutic vulnerability and support further investigation of mitochondria-centered therapeutic strategies for GC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1445-1462"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKM2 is the Metabolic Checkpoint for Stemness Features in Head and Neck Cancer.","authors":"Wan-Hsuan Sun, Ta-Jung Peng, Hsueh-Jou Fang, Chia-Ling Chang, Yu-Wen Tang, Kuang-Hui Sun","doi":"10.7150/jca.132595","DOIUrl":"10.7150/jca.132595","url":null,"abstract":"<p><p>Owing to their self-renewal, differentiation capabilities, and increased chemoresistance, cancer stem cells (CSCs) are associated with poor prognosis and an elevated chance of relapse and metastasis. CSCs survive under therapy-imposed pressure and aggravate tumor malignancy through metabolic reprogramming, leading to treatment failure. The RNA level of pyruvate kinase isoenzyme M2 (<i>PKM2</i>) is increased in head and neck cancer (HNC) tissues and is linked to poor prognosis, whereas <i>PKM2</i> deletion was found to accelerate tumorigenesis and tumor growth <i>in vivo</i>, leading to a paradox between <i>PKM2</i> expression and tumorigenesis. To date, the role of PKM2 inhibition in HNC progression remains unclear. In the present study, we found that low PKM2 protein expression was significantly associated with later stages and higher grades of cancer in HNC tissues. Following <i>PKM2</i> silencing, HNC cells exhibited significantly increased ATP levels, decreased lactate production, and upregulated mitochondrial respiratory activity. In addition, <i>PKM2</i> knockdown promoted clonogenicity, motility, nuclear-activated β-catenin, CSC formation, and <i>in vivo</i> tumorigenicity in HNC cells. PKM2 inhibition further augmented stemness and resistance to chemotherapeutic drugs in HNC CSCs. Whole-genome transcriptome analysis of <i>PKM2</i>-knockdown CSCs revealed upregulation of differentially expressed genes (DEGs) in the Wnt signaling pathway. The present study concluded that decreased PKM2 is associated with aggressive clinicopathological features. PKM2 inhibition-promoted stemness may be mediated by increased nuclear β-catenin localization, which potentially contributes to tumorigenesis and disease progression in HNC. Our findings suggest that PKM2 modulates HNC stemness by linking metabolic rewiring with oncogenic signaling, highlighting its potential as a molecular target for adjuvant therapy in patients with HNC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1504-1519"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental co-exposure to microplastics and phenol may influence redox signaling and tumor microenvironment dynamics.","authors":"Chung-Yu Lin, Che-Hsin Lee","doi":"10.7150/jca.135514","DOIUrl":"10.7150/jca.135514","url":null,"abstract":"<p><p>Environmental exposure patterns have shifted from single-compound exposure to complex co-exposure scenarios. Among widespread pollutants, microplastics (MPs) and phenol may interact biologically despite their distinct physicochemical properties. Phenol is associated with oxidative stress-related toxicity, whereas MPs may serve as potential carriers and redox-active modifiers. This review proposes that MP-induced oxidative stress and phenol-mediated antioxidant disruption may jointly reshape redox-sensitive intracellular signaling under MPs-phenol co-exposure conditions, with mitogen-activated protein kinase (MAPK) pathways proposed as potential convergence nodes. Within this framework, MAPK signaling may link oxidative stress to hypoxia-inducible factor 1α (HIF-1α) stabilization, angiogenic responses, and tumor-associated processes, and may also facilitate NF-κB/STAT3-mediated inflammatory signaling and PD-L1 regulation. Because direct experimental evidence for these integrated mechanisms remains limited, this framework should be regarded as a biologically plausible and testable model rather than a confirmed causal pathway. This review highlights key knowledge gaps and future priorities for evaluating how complex environmental co-exposures may influence cancer progression and immune regulation.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1470-1479"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}