Cancer Biology & Therapy最新文献

{"title":"Advances in natural killer cell immunotherapy for hematologic malignancies.","authors":"Huijie Hu, Yan Xiong, Minxin Xia, Lixia Sheng","doi":"10.1080/15384047.2026.2658896","DOIUrl":"10.1080/15384047.2026.2658896","url":null,"abstract":"<p><p>Natural killer (NK) cells are a unique subset of cytotoxic lymphocytes within the innate immune system. They play a pivotal role in antiviral and antitumor immunity. NK cell-based adoptive immunotherapy has advanced rapidly in recent years. Innovative approaches, such as autologous/haploidentical NK cell infusion, chimeric antigen receptor NK cells, and NK cell engagers, have emerged, demonstrating promising potential in the treatment of various diseases. Currently, enhancement strategies for NK cell therapy primarily focus on two key aspects: improving expansion efficiency and persistence, with a positive effect on the therapy's potency and cytotoxic efficacy. The present review systematically introduces the functional mechanisms of NK cells and their specialized functional subsets. This review discusses the progress and optimization methods of NK cell therapy and provides an outlook on future research directions.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2658896"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE2S promotes gastric cancer progression through RACGAP1 stabilization associated with K292-dependent K63-linked ubiquitination.","authors":"HeFei Cheng, Ziqing Zhou, Qirun Cheng, Ziqi Sui","doi":"10.1080/15384047.2026.2737476","DOIUrl":"10.1080/15384047.2026.2737476","url":null,"abstract":"<p><strong>Objective: </strong>Gastric cancer (GC) remains highly lethal, and effective molecular targets are limited. This study investigated the expression, exploratory survival associations, and mechanistic role of UBE2S in GC.</p><p><strong>Methods: </strong>UBE2S expression and survival associations were analyzed using public datasets, whereas UBE2S protein expression was assessed in seven paired GC tissues and GC cell lines. Loss- and gain-of-function assays, xenograft models, quantitative proteomics, genetic rescue, JNK inhibition, co-immunoprecipitation, cycloheximide chase, proteasome inhibition, and linkage-specific ubiquitination assays were performed.</p><p><strong>Results: </strong>UBE2S was upregulated in GC and showed apparent within-dataset discriminatory ability at the tissue-transcript level (AUC = 0.909); higher expression showed an exploratory association with unfavorable survival in public datasets. Protein assessment in seven paired tissues was consistent with this expression pattern. UBE2S depletion suppressed GC cell viability, clonogenicity, migration, and xenograft growth. Proteomics prioritized RACGAP1 as a candidate downstream effector, and subsequent rescue experiments supported its functional relevance. UBE2S associated with RACGAP1 and increased RACGAP1 protein stability without altering its mRNA expression. UBE2S depletion decreased K63-linked and increased K48-linked ubiquitination of RACGAP1, whereas MG132 partially restored RACGAP1 abundance. K292 mutation impaired UBE2S-dependent K63-linked ubiquitination, RACGAP1 accumulation, JNK/c-Jun activation, and malignant phenotypes, although RACGAP1-K292R retained partial activity. Pharmacological JNK inhibition with SP600125 suppressed RACGAP1-mediated JNK/c-Jun reactivation and clonogenic rescue.</p><p><strong>Conclusion: </strong>Our findings support a model in which UBE2S promotes GC progression by stabilizing RACGAP1 in association with K292-dependent K63-linked ubiquitination, providing a mechanistic basis for further preclinical investigation of the UBE2S/RACGAP1/JNK/c-Jun axis.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2737476"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARHGAP40 suppresses clear cell renal cell carcinoma progression and is associated with altered glutamine-related metabolism and redox balance.","authors":"Na You, Xiaoxia Wang, Caizhu Wang, Long Ma, Yanli Lyu, Han Liu, Fan Yang, Jiandong Wang, Longjiang Zhang, Jufang Wang","doi":"10.1080/15384047.2026.2746137","DOIUrl":"10.1080/15384047.2026.2746137","url":null,"abstract":"<p><strong>Objective: </strong>Clear cell renal cell carcinoma (ccRCC) is characterized by marked molecular and metabolic heterogeneity. This study investigated the functional role of ARHGAP40 in ccRCC and examined signaling and metabolic changes associated with ARHGAP40 expression.</p><p><strong>Methods: </strong>TCGA-KIRC and DiseaseMeth datasets were used to analyze ARHGAP40 expression and promoter methylation. Gain- and loss-of-function experiments evaluated malignant phenotypes <i>in vitro</i>, and an ARHGAP40-overexpression xenograft model was used to assess tumor growth. Co-immunoprecipitation and RhoA activity assays assessed ARHGAP40-RhoA interaction and RhoA activation, while PI3K/AKT signaling, glutamine metabolism, GSH/GSSG, and ROS levels were examined. Rescue experiments were performed using SC79, RhoA-Q63L, and NAC.</p><p><strong>Results: </strong>ARHGAP40 was downregulated in ccRCC and was associated with increased promoter methylation. ARHGAP40 overexpression suppressed cell proliferation, migration, invasion, EMT, and xenograft growth, while promoting apoptosis and G1-phase arrest; ARHGAP40 knockdown produced the opposite effects. Mechanistically, ARHGAP40 was associated with RhoA, and its overexpression was accompanied by reduced RhoA activity and PI3K/AKT phosphorylation. ARHGAP40 overexpression also reduced intracellular glutamine and glutamate levels and net glutamine consumption, decreased the GSH/GSSG ratio, and increased ROS levels. SC79 and RhoA-Q63L partially reversed the biological and redox effects induced by ARHGAP40 overexpression, whereas NAC reversed the redox changes.</p><p><strong>Conclusion: </strong>ARHGAP40 acts as a tumor suppressor in ccRCC. Our findings support a functional link between ARHGAP40, RhoA-PI3K/AKT signaling, glutamine-related metabolism, and cellular redox balance.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2746137"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parthenolide inhibits the progression of intrahepatic cholangiocarcinoma by promoting ferroptosis through inhibiting UBD.","authors":"Yuanzhu Xie, Jia Wang, Jia Zhou, Yuhuai Peng, Yizhi Wang, Yueren Wang, Yinghui Song","doi":"10.1080/15384047.2026.2664327","DOIUrl":"10.1080/15384047.2026.2664327","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the antitumor activity and molecular mechanism of Parthenolide (Par) against intrahepatic cholangiocarcinoma (ICC), a highly malignant liver tumor with poor prognosis, to explore potential new treatment strategies.</p><p><strong>Methods: </strong>Par was identified through screening an FDA compound library. <i>In vitro</i> assays were performed to assess its effects on ICC cell proliferation, colony formation, invasion, migration, cell cycle, and apoptosis. An <i>in</i> <i>vivo</i> nude mouse tumor model was used to evaluate tumor growth inhibition. Transcriptomic analysis, molecular docking, and cellular thermal shift assays were employed to identify key targets and pathways. Changes in ferroptosis-related markers, including iron ion levels, lipid peroxides, SOD activity, and GPX4 expression, were measured. Rescue experiments with the ferroptosis inhibitor ferrostatin-1 were conducted to validate the role of ferroptosis.</p><p><strong>Results: </strong>Par significantly inhibited ICC cell proliferation, colony formation, invasion, and migration, induced G2/M phase arrest, and promoted apoptosis <i>in vitro</i>; and suppressed tumor growth <i>in vivo</i>. Transcriptomic analysis showed upregulation of HMOX-1 and downregulation of Ubiquitin D (UBD) after Par treatment. Par was confirmed to bind to the UBD protein. Enrichment analysis indicated ferroptosis as a key pathway, with Par treatment leading to increased iron ions, lipid peroxide accumulation, reduced SOD activity, and downregulated GPX4. Ferrostatin-1 partially reversed Par-induced inhibitory effects.</p><p><strong>Conclusion: </strong>This study demonstrates for the first time that Par exerts anti-ICC effects related to inhibition of UBD, thereby activating the ferroptosis pathway. These findings provide a novel potential strategy and therapeutic target for ICC treatment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2664327"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing progesterone receptor modulation in glioblastoma: from <i>in vitro</i> and animal model to a human pilot protocol.","authors":"Denisse Arcos-Montoya, Patricia García-López, Talia Wegman-Ostrosky, Ignacio Camacho-Arroyo, Silvia Anahí Valdés-Rives, Claudia Bello-Alvarez, Joaquín Manjarrez-Marmolejo, Marisol De La Fuente-Granada, Alejandro Ordaz-Ramos, Daniela Ávila-González, Néstor Fabián Díaz, Carlos Fabricio Guadarrama-Rangel, Andrés Mauricio Bonilla Navarrete, Orwa Aboud, David F Cantú-de-León, Bernardo Cacho-Díaz, Aliesha González-Arenas","doi":"10.1080/15384047.2025.2603095","DOIUrl":"10.1080/15384047.2025.2603095","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, including glioblastomas (GB) and high-grade astrocytomas (HGA), are the most common brain tumors in adults, with poor survival rates around 15 months. Hormonal factors, particularly progesterone receptor (PR) activation, promote tumor growth. Current treatment involves surgery, radiotherapy and chemotherapy (temozolomide), but survival rates remain low. Repurposing mifepristone (MF), a contraceptive drug, shows promise for GB treatment, warranting further study.</p><p><strong>Methods: </strong>PR expression in U87, U251 and C6 cell lines were assessed using immunofluorescence and Western Blot. PR isoforms were quantified by densitometry. Progesterone (P4) and 5α-dihydroprogesterone (5α-DHP) synthesis were evaluated using LC/MS. MF's effect on cell viability was determined by IC₅₀ and IC₂₀ values. Its impact on non-tumoral cells and 3D glioma sphere formation was also analyzed. The effects of <i>in situ</i> administration of MF were assessed <i>in vivo</i> using a rat model with C6 glioma implants. Clinical outcomes were evaluated in GB patients receiving MF alongside standard treatment.</p><p><strong>Results: </strong>PR was predominantly nuclear in all cell lines, with U87 showing the highest PR-B isoform levels. Only U251 synthesized 5α-DHP significantly. MF reduced viability in U251, U87 and C6 cells without affecting non-tumoral cells. Sphere formation efficiency decreased with MF treatment. In rats, MF reduced tumor volume dose-dependently. Clinically, MF improved patient survival from 165 to 588days and enhanced quality of life without severe adverse effects.</p><p><strong>Conclusion: </strong>MF effectively reduces GB cell viability, sphere formation efficacy and tumor volume. These findings support further investigation of MF as a therapeutic strategy in GB treatment.</p><p><strong>Précis (condensed abstract): </strong>Our research highlights the critical role PR in GB progression using <i>in vitro</i> and <i>in vivo</i> models. MF, a PR modulator, effectively reduced cell viability and sphere formation in cellular assays and significantly decreased tumor volume in an <i>in vivo</i> study. The pilot trial demonstrated the pharmacological safety of using MF as an adjuvant in GB treatment. Patients treated with MF showed a significant increase in survival, with an 80% survival rate at 1 year compared to 0% in those who were treated with the standard treatment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2603095"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma.","authors":"Yudi Liu, Ling Xiao, Xinyu Nie, Jiahua Lyu, Chengxi Tang, Linjie Li, Xue Zhang, Tao Li, Jianming Huang, Shichuan Zhang","doi":"10.1080/15384047.2025.2610526","DOIUrl":"10.1080/15384047.2025.2610526","url":null,"abstract":"<p><strong>Background: </strong>The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized.</p><p><strong>Methods: </strong>We investigated Lenvatinib's effects on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs via Western blot, VEGFA expression via RT-qPCR/ELISA, and angiogenesis via immunofluorescence. LUAD-HUVEC crosstalk was modeled in vitro. In C57BL/6 mice bearing LUAD tumors, we evaluated the efficacy of RT and anti-PD-L1 with or without Lenvatinib, monitoring tumor growth, survival, and profiling the tumor microenvironment by mIHC and flow cytometry.</p><p><strong>Results: </strong>Lenvatinib suppressed radiation-induced PD-L1 and VEGFR2 expression, inhibited angiogenesis, and disrupted HUVEC-facilitated LUAD proliferation. The triple-combination (RT + anti-PD-L1 + Lenvatinib) significantly suppressed tumor progression (<i>P</i> < 0.05) and extended median survival (34 vs. 29.5 days, <i>P</i> < 0.05) versus dual therapy. It also enhanced intratumoral CD8⁺ T-cell infiltration and cytotoxicity, promoted M1-like macrophage polarization, and reduced regulatory T cell frequency and microvessel density.</p><p><strong>Conclusions: </strong>Lenvatinib potentiates RT and anti-PD-L1 therapy in LUAD through dual immune-vascular modulation, supporting the clinical translation of this triple-combination strategy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2610526"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12773621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular mechanisms of platelets in tumor invasion and metastasis: a controversial role.","authors":"Amir Hossein Kheirkhah, Tahereh Zarei Taher, Zahra Khosrowpour, Omid Mahmoudian, Maria Kavianpour","doi":"10.1080/15384047.2026.2692154","DOIUrl":"10.1080/15384047.2026.2692154","url":null,"abstract":"<p><p>Platelets, traditionally recognized for their role in hemostasis, are now understood to actively contribute to tumor progression, angiogenesis, and metastasis. Through dynamic bidirectional interactions with cancer cells, platelets undergo measurable alterations in count, mean platelet volume, and molecular cargo, including proteins and mRNAs, supporting their potential utility as liquid biopsy biomarkers for early cancer detection. Within the tumor microenvironment, platelets contribute to immune evasion, support tumor cell intravasation and extravasation, enhance the survival of circulating tumor cells, and promote neovascularization. In addition, they can physically shield malignant cells from immune surveillance, thereby increasing metastatic potential. Although context-specific anti-tumor effects have been reported, the predominant evidence supports a largely pro-tumorigenic and pro-metastatic role for platelets. Elucidating the molecular mechanisms underlying platelet-tumor interactions is therefore essential for improving cancer risk stratification, prognostic evaluation, and therapeutic development. This review summarizes current advances in platelet-derived biomarkers and discusses emerging therapeutic strategies targeting platelet-mediated pathways to suppress metastasis and improve clinical outcomes in cancer patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2692154"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and prognostic value of lncSPATA8-AS1 in prostate cancer and its regulatory effect on tumor progression.","authors":"Jinman Zhong, Yanmeng Deng, Xingru Qin, Quanxin Yang","doi":"10.1080/15384047.2026.2678636","DOIUrl":"10.1080/15384047.2026.2678636","url":null,"abstract":"<p><strong>Background: </strong>Long noncoding RNAs (lncRNAs) have significant impacts on the occurrence and development of many cancers. However, their effects and mechanisms on prostate cancer (PCa) remain largely unknown. The study was to explore the influence of lncSPATA8-AS1 on PCa and its molecular mechanism of action.</p><p><strong>Methods: </strong>In the GSE179321 dataset, lncSPATA8-AS1, which was upregulated in PCa tumor tissues, was selected. The expression levels of lncSPATA8-AS1, miR-328-5p, and EPHB2 were detected using RT-qPCR. <i>In vitro</i> experiments were conducted to investigate the effects of lncSPATA8-AS1 on the malignant biological behaviors of PCa cells. Finally, the mechanism of lncSPATA8-AS1 was revealed through methods such as biotin-labeled RNA pull-down, luciferase assay, and rescue experiments.</p><p><strong>Results: </strong>LncSPATA8-AS1 was upregulated in PCa tissues, serum, and cell lines. Clinically, lncSPATA8-AS1 could serve as a biomarker for the diagnosis and prognosis of PCa. Silencing lncSPATA8-AS1 can inhibit the cell viability of PCa tumor cells, suppress epithelial-mesenchymal transformation (EMT), cell migration, and invasion. Mechanistically, lncSPATA8-AS1 affects the expression of EPHB2 by interacting with miR-653-5p, thereby regulating the malignant biological behavior of PCa.</p><p><strong>Conclusion: </strong>The expression of lncSPATA8-AS1 is upregulated in the serum of PCa patients, and it has great potential as a biomarker for the diagnosis and prognosis of PCa. The lncSPATA8-AS1/miR-328-5p/EPHB2 axis drives the malignant biological behavior of prostate cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2678636"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thioredoxin reductase-1 facilitates cellular plasticity and stemness mediated by TGF-β1 in non-small cell lung cancer.","authors":"Yaw-Dong Lang, Shin-Yuan Gu, Jou-Ho Shih, Chun-Jung Lin, Hua-Hsin Chiang, Tsai-Yu Lin, Yu-Ching Lee, Keng-Chang Tsai, Jui-Tin Chang, Cheng-Ying Chu, Yuh-Shan Jou, Teh-Ying Chou","doi":"10.1080/15384047.2026.2724630","DOIUrl":"10.1080/15384047.2026.2724630","url":null,"abstract":"<p><strong>Background: </strong>Cellular plasticity and epithelial-mesenchymal transition (EMT) promote the initiation and progression of non-small cell lung cancer (NSCLC). Thioredoxin reductase 1 (TXNRD1), a key redox enzyme, has been linked to malignancy, but its mechanism in NSCLC remains unclear. We examined whether TXNRD1 regulates TGF-β1 autocrine signaling to drive EMT and stemness.</p><p><strong>Materials: </strong>Stage-progression gene profiles were analyzed in the TCGA and GEO databases with an emphasis on redox gene families. TXNRD1 was manipulated by overexpression or knockdown in A549, H226, and H1299 cells, followed by migration/invasion, spheroid assays, ELISA for cytokines, and RT-qPCR/Western blot for EMT markers. RNA-seq with pathway enrichment analyses was used to identify downstream programs. An orthotopic lung cancer mouse model was established using TXNRD1-WT cells, TXNRD1-deficient cells, and TXNRD1-deficient cells treated with TRi-1. Tumor progression was monitored by bioluminescence imaging at 6 and 12 weeks after transplantation.</p><p><strong>Results: </strong>TXNRD1 expression was ~2-fold higher in advanced-stage NSCLC and was validated in tumor tissues. CRISPR/Cas9 or siRNA knockdown reduced EMT-associated genes and decreased TGF-β1 production in A549 and H226 cells. TXNRD1 overexpression increased EMT and stemness markers and produced larger, more compact spheres with higher sphere numbers in H1299 cells. RNA-seq indicated the TXNRD1 pathway activates the TGF-β1 pathway to promote EMT, motility, and stemness via an autocrine loop; knockdown or TXNRD1 inhibition suppressed metastatic tumor growth in vivo.</p><p><strong>Conclusions: </strong>Our study identifies TXNRD1 as a crucial regulator of cellular plasticity and metastasis in NSCLC via the TGF-β1 pathway, suggesting that targeting TXNRD1 may reduce metastatic potential and improve patient survival.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2724630"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic silencing <i>L3MBTL4</i> sensitizes esophageal cancer to DNA-PKcs inhibitor.","authors":"Yuan Li, Aiai Gao, Yuanxin Yao, Meiying Zhang, Lianlian Jin, Qian Tao, Mingzhou Guo","doi":"10.1080/15384047.2026.2646393","DOIUrl":"10.1080/15384047.2026.2646393","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) remains a deadly disease, with no effective therapeutics available for advanced stages. The application of the \"synthetic lethality\" principle to cancers with abnormal epigenetic changes provides more opportunities for developing novel therapeutic strategies. It is necessary to identify more molecules that are involved in the DNA damage repair response or cell fate determination to reach this end. Malignant brain tumor (MBT) domain proteins are important for development and cell fate. <i>L3MBTL4</i> is a new member of this family, but its function remains to be clarified.</p><p><strong>Methods: </strong>Lentiviral infection was used to re-express <i>L3MBTL4</i>. Immunoprecipitation, immunofluorescence, comet, homologous recombination (HR), and non-homologous end joining (NHEJ) reporter assays were performed to explore the mechanism involved.</p><p><strong>Results: </strong>The expression of <i>L3MBTL4</i> was regulated by methylation of the promoter region. <i>L3MBTL4</i> inhibited cell proliferation and colony formation, and induced G1/S arrest and apoptosis in ESCC cells. <i>L3MBTL4</i> promoted ATM signaling and inhibited NHEJ signaling by interacting with KU70. Epigenetic silencing of <i>L3MBTL4</i> sensitized ESCC cells to NU7441, a DNA-PKcs inhibitor, both <i>in vitro</i> and <i>in vivo.</i></p><p><strong>Conclusion: </strong><i>L3MBTL4</i> is a potential tumor suppressor and methylation of <i>L3MBTL4</i> is a sensitive marker of DNA-PKcs inhibitors.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2646393"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}