Ask about this productRelated genes to: DLAT antibody
- Gene:
- DLAT NIH gene
- Name:
- dihydrolipoamide S-acetyltransferase
- Previous symbol:
- DLTA
- Synonyms:
- PDC-E2, E2
- Chromosome:
- 11q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-30
- Date modifiied:
- 2018-12-14
Related products to: DLAT antibody
Related articles to: DLAT antibody
- Immunotherapy has reshaped cancer treatment, yet its efficacy in many solid tumors remains limited by an immunosuppressive microenvironment and insufficient antigen presentation. As a central gatekeeper of antitumor immunity, the cGAS-STING pathway represents a key axis for converting tumor-intrinsic stress into productive immune priming. Here, we propose an integrated strategy that couples immunogenic tumor cell death with tumor-restricted cGAS-STING activation and adjuvant-amplified innate signaling. Cuproptosis, a recently identified copper-dependent cell-death program, can act as an endogenous trigger of tumor-intrinsic cGAS-STING activation, providing a promising avenue to link cytotoxicity with immune stimulation. We engineered a biomimetic, tumor-responsive nanoplatform (Cu-R837@CM) by co-assembling Cu with the TLR7 agonist R837 and cloaking the core with homologous tumor cell membranes to enhance tumor targeting and intratumoral retention. In vitro, Cu-R837@CM released Cu under acidic conditions, inducing glutathione depletion and ROS accumulation, promoting DLAT aggregation and mitochondrial dysfunction, increasing intracellular 2'3'-cGAMP, and activating cGAS-STING signaling. Concurrently, R837 enhanced dendritic-cell maturation and cytokine production, thereby improving antigen presentation. In vivo, Cu-R837@CM markedly inhibited tumor growth, increased CD4/CD8 T-cell infiltration, and remodeled the tumor immune microenvironment toward an antitumor phenotype. Notably, combining Cu-R837@CM with PD-L1 blockade achieved complete tumor regression and significantly prolonged survival. Collectively, Cu-R837@CM offers a clinically translatable nanoadjuvant paradigm that integrates cuproptosis-driven cGAS-STING activation with TLR7 co-stimulation for hepatocellular carcinoma immunotherapy. - Source: PubMed
Publication date: 2026/06/10
Jing LinhaoZhao ShuaijunSun ChenguangCui FangfangXia YaningShi YupengWang Weijie - Chemoresistance remains a major barrier in treating oral squamous cell carcinoma (OSCC). This study investigated whether the marine-derived sesterterpenoid heteronemin (HET) suppresses chemoresistant OSCC (SAS-CR) cells and elucidated its underlying mechanisms. HET dose- and time-dependently reduced SAS-CR viability, inhibited clonogenic growth, and exhibited stronger cytotoxicity than cisplatin or 5-fluorouracil. Furthermore, HET induced S-phase arrest by downregulating proliferation and cell-cycle proteins (PCNA, c-Myc, cyclin A, cyclin D3, CDK4, and CDK6). Concurrently, it triggered intrinsic apoptosis, characterized by mitochondrial depolarization, upregulated cleaved caspase-3/PARP and Bax, and downregulated Bcl-2. This caspase-dependent apoptosis was partially reversed by pan-caspase inhibitor Z-VAD-FMK. Transcriptomic profiling linked these phenotypes to metabolic stress, revealing alterations in the tricarboxylic acid cycle, mitochondrial respiration, and copper homeostasis. Consistently, HET elevated intracellular Cu levels and reduced FDX1, SDHB, and lipoylated DLST/DLAT protein expression-cytotoxic effects that were attenuated by the copper chelator tetrathiomolybdate (TTM). Additionally, HET increased reactive oxygen species (ROS) production, whereas ROS scavenger N-acetylcysteine (NAC) attenuated HET-induced apoptosis and restored cuproptosis-related markers. In a zebrafish model, HET demonstrated negligible toxicity while reducing tumor-associated fluorescence and FDX1 expression. Collectively, HET effectively suppresses chemoresistant OSCC through coordinated ROS-dependent apoptosis and cuproptosis-associated mitochondrial stress, supporting its development as a therapeutic candidate for refractory OSCC. - Source: PubMed
Publication date: 2026/06/18
Huang Chiung-WeiLin Fan-LiChang Chun-FengHuang Hsiao-HsuanWu Wan-JuChang Hui-MinLin Mei-YingHsu Jue-LiangHung Shih-YaLee Chien Hsing - Breast cancer exhibits a profoundly immunosuppressive tumor microenvironment (TME), where innate immune silence prevents antigen sensing and persistent T cell exhaustion limits effector responses, rendering most immunotherapies ineffective. Clinical profiling of 1093 The Cancer Genome Atlas (TCGA) cases identified a glucose-fueled glutathione (GSH)-glutathione peroxidase 4 (GPX4)-dihydrolipoamide S-acetyltransferase (DLAT) axis as a dominant metabolic shield that suppresses oxidative stress, and thereby enforces both stimulator of interferon genes (STING) silence and CD8 T cell exclusion. To dismantle this barrier, we developed an immunometabolic nanotherapy, GOx/ES-CO-LDH@TIGIT-Nanotrap (TNT). In acidic tumors, proton-driven layered double hydroxide (LDH) disassembly releases glucose oxidase (GOx) and extremely small cuprous oxide (ES-CO). GOx depletes glucose and nicotinamide adenine dinucleotide phosphate (NADPH) to induce disulfidptosis, while ES-CO releases cuprous ions (Cu) that trigger cuproptosis via binding to lipoylated mitochondrial proteins. Their mutual biochemical amplification produces a cycloacclerated disulfidptosis-cuproptosis cascade that collapses the GSH-GPX4-DLAT axis and restores STING activation. Meanwhile, the macrophage-derived T cell immunoreceptor with Ig and ITIM domains (TIGIT) Nanotrap sequesters CD155 to prevent T cell suppression. Together, this coordinated innate reactivation and adaptive rescue converts immune-cold tumors into STING-inflamed and T cell responsive lesions. - Source: PubMed
Publication date: 2026/06/18
Guo ShuaiWang XiaokeChen HuiwanChen XiaopanLi TianyuShi XueqinOu BaoyanYuan JuntaoYang ZhiluZhou JunDeng ShaohuiLiu YangLiang Xing-JieOu Caiwen - Despite advances in oncology, the dual challenge of achieving precise tumor-targeted therapy while simultaneously activating antitumor immunity remains a major clinical barrier. In this study, we engineered a biocompatible copper-based platform, hyaluronic acid (HA) modified Cu ions based therapeutic (B-Cu/HA), that integrates selective tumor targeting, intrinsic cytotoxicity, and immune activation within a single therapeutic system. Leveraging the HA-CD44 interaction, B-Cu/HA exhibited preferential accumulation and prolonged retention in CD44-overexpressing tumors, while maintaining an excellent biosafety profile. Across multiple cancer models, B-Cu/HA robustly inhibited tumor progression. Mechanistically, it induced cuproptosis through upregulation of FDX1 and aggregation of lipoylated DLAT, and triggered ROS-mediated activation of the cGAS-STING pathway, promoting immunogenic cell death. Transcriptomic analysis revealed activation of hypoxia and cytokine signaling pathways, aligning with enhanced CD8 T-cell cytotoxicity and remodeling of the tumor immune microenvironment. The animal models studies demonstrated that B-Cu/HA significantly suppressed tumor growth without systemic toxicity, and synergistically enhanced the efficacy of the immune checkpoint inhibitors anti-TIGIT. Together, these findings establish B-Cu/HA as a multifunctional, immunomodulatory formulation that offers a clinically translatable strategy to enhance tumor immunotherapy and overcome resistance in CD44-overexpressing tumors. - Source: PubMed
Publication date: 2026/06/13
Fang YifengTu MengyanTu XinruZhang HongboLi YangyangXu Junfen - Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity characterised by coronal curvature, axial rotation, and altered trunk translation. Radiographic indices (e.g., Cobb angle) quantify structure but incompletely represent functional correctability, a core target of physiotherapeutic scoliosis-specific exercises (PSSE). Side-Shift Therapy (SST), originating from the RNOH tradition (Mehta, 1985) and operationalised via a mobility classification (Betts et al., 2014), is a voluntary lateral translation of the trunk relative to the pelvis (not a side-bend). This paper presents a biomechanics-first teaching framework linking functional spinal unit (FSU) mechanics, thoracic ring behaviour, motor control sequencing, and growth-modulation hypotheses. FSUs are modelled as 6-DOF systems with translation-rotation coupling; in simplified terms, Ktt represents resistance to translation and Ktr represents how rotation changes when translation is performed (short note: coupling = rotation response during translation). Load-path optimisation is framed via an apical bending moment approximation M ≈ Fg·dlat (dlat = lateral moment arm). Time-under-load is explained using viscoelastic forms where eta captures time-dependence. In growing spines, a Hueter-Volkmann-type simplification gdot = g0 - ksigma is used to describe stress-sensitive growth (k = stress sensitivity). Clinically, original mobility Types (1: beyond midline; 2: to midline; 3: cannot reach midline) are retained with reported substantial reliability (kappa ≈ 0.76-0.77). A multiplanar update adds transverse modifiers for Types 1-2: A (rotation reduces), B (rotation persists), C (rotation worsens), providing a pragmatic proxy for coupling behaviour and thoracic compliance. The framework supports stratified PSSE prescription and outlines testable targets for reliability, responsiveness, and predictive validity. - Source: PubMed
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