Ask about this productRelated genes to: NT5E antibody
- Gene:
- NT5E NIH gene
- Name:
- 5'-nucleotidase ecto
- Previous symbol:
- NT5
- Synonyms:
- CD73, eN, eNT, CALJA
- Chromosome:
- 6q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 1989-02-23
- Date modifiied:
- 2016-10-05
Related products to: NT5E antibody
Related articles to: NT5E antibody
- Metastatic castration-resistant prostate cancer (mCRPC) remains a leading cause of cancer-related mortality in men. Although poly(ADP-ribose) polymerase inhibitors (PARP inhibitor) are approved for mCRPC patients with homologous recombination repair (HRR) deficiencies, clinical trials combining Olaparib with PD-1/PD-L1 inhibitors have shown limited efficacy in unselected populations. To investigate the immunomodulatory effects of PARP inhibitor in an unbiased manner, we performed bulk RNA sequencing on HRR-proficient MycCaP cells treated with the PARP inhibitor (Olaparib) versus vehicle control. Transcriptomics analysis revealed robust upregulation of CD73 (NT5E), an ectoenzyme and emerging immune checkpoint that generates extracellular adenosine, suggesting an adaptive mechanism that undermines Olaparib efficacy and promotes immunosuppression. CD73 induction by Olaparib was validated in both human and mouse prostate cancer cell lines, with more pronounced effects in HRR-compromised PTEN knockout (KO) cells. Mechanistically, olaparib-driven CD73 expression was mediated through DNA damage-activated ATR-CHEK1-IRF1 and TGF-β1-AKT signaling pathways. In parallel, Olaparib enhanced tumor immunogenicity by activating type I interferon (IFN) signaling and antigen presentation machinery. In vivo, combining olaparib with CD73 blockade significantly delayed tumor growth, improved T-cell infiltration, and augmented CD8⁺ T-cell effector function across HRR-proficient and PTEN KO prostate cancer models. These findings identify Olaparib-induced CD73 upregulation as an adaptive resistance mechanism and support Olaparib plus CD73 blockade as a promising therapeutic strategy for advanced prostate cancer, irrespective of HRR status. - Source: PubMed
Publication date: 2026/08/18
Xie PingMa RenqiangZhang MinghuiFan JieTang HuiSong LongzhenWan YongKuzel Timothy MFang DeyuCui WeiguoWu Jennifer DAbdulkadir Sarki AZhang YiPatnaik AkashZhang Bin - CD73, encoded by NT5E, is an ecto-5'-nucleotidase implicated in tumour progression, but its association with glycolysis-related metabolic features in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we combined public transcriptomic analyses with in vitro and in vivo experiments to investigate the relationship between NT5E/CD73 and these features in HNSCC. NT5E expression was positively associated with glycolysis-related signatures, and a high glycolysis score was associated with poorer overall survival in an exploratory analysis. In CAL27 cells, NT5E knockdown reduced extracellular acidification rate and oxygen consumption rate and decreased the expression of glucose transporter 3 (GLUT3), lactate dehydrogenase A (LDHA) and pyruvate kinase M2 (PKM2), indicating a broader reduction in metabolic activity. In a xenograft model, NT5E depletion suppressed tumour growth and reduced GLUT3, LDHA and PKM2 expression. ADORA2B was upregulated in HNSCC, and its silencing decreased glycolysis-related gene expression, whereas pharmacological activation of A2B partially restored glycolysis-related protein expression and migratory capacity after NT5E knockdown. These findings support an association between NT5E/CD73 and glycolysis-related metabolic features in HNSCC and suggest that A2B signalling may contribute, at least in part, to the associated metabolic and migratory changes. - Source: PubMed
Publication date: 2026/08/17
Zhang HanwenGao ChangXue FeifeiShao WeihuaZhang LeqiFan YiYuan Hua - The therapeutic landscape of advanced melanoma has been transformed by immune checkpoint inhibitors (ICIs); however, primary and acquired resistance remain formidable challenges for a substantial subset of patients. Emerging evidence identifies the CD73-adenosine axis as a critical "metabolic immune checkpoint" that orchestrates an immunosuppressive tumor microenvironment (TME). This review systematically explores the biochemical cascade in which extracellular ATP is converted into immunosuppressive adenosine by the sequential action of ectonucleotidases CD39 and CD73. We detail the multidimensional regulation of CD73 expression, driven by a convergence of environmental stressors such as hypoxia-stabilized HIF-1α, oncogenic MAPK signaling, and pro-inflammatory cytokines including TGF-β and TNF-α. Furthermore, we evaluate the clinical utility of CD73 as a prognostic and predictive biomarker, highlighting the dichotomous significance of its expression on tumor versus immune cells and the potential of liquid biopsy-based monitoring via soluble CD73 activity and melanoma-derived exosomes (MTEX). Finally, we discuss therapeutic strategies to dismantle this metabolic barrier, ranging from monoclonal antibodies and small-molecule inhibitors to synergistic combinations with ICIs, targeted therapies, and next-generation cellular engineering utilizing CRISPR/Cas9-mediated gene editing. Integrating adenosinergic blockade into the framework of precision immuno-oncology represents a pivotal dimension in overcoming treatment resistance and improving clinical outcomes for patients with melanoma. - Source: PubMed
Publication date: 2026/07/30
Liu XiaotingSun PengchengChen CanChen Xi - CD73 is an enzyme that generates extracellular adenosine and has been implicated in tumor-associated immune suppression, but its biological and clinical significance in pancreatic ductal adenocarcinoma (PDAC) remains incompletely understood. We investigated the prognostic relevance and biological functions of CD73 in PDAC using transcriptomic analyses, functional assays, and mouse models. Transcriptomic analyses consistently showed that CD73 expression was correlated with hypoxia, glycolysis related, and cell-cycle programs. In agreement with these findings, hypoxic exposure induced CD73 mRNA expression in a subset of PDAC cell lines, and CD73 knockdown modestly affected glycolysis related extracellular acidification (ECAR) in a cell line dependent manner, and modulation of CD73 expression altered PDAC cell growth. CD73 expression was also associated with reduced intratumoral CD8 T cell infiltration and cytolytic activity in human PDAC cohorts. , CD73 overexpression accelerated cancer progression and shortened survival in immunocompetent mice, whereas this effect was abrogated in immunodeficient NSG mice. Flow cytometric analysis further demonstrated reduced intratumoral CD8 T cell infiltration in CD73 overexpressing tumors. Clinically, high CD73 expression was consistently associated with worse survival in multiple PDAC cohorts. Collectively, these findings suggest that CD73 is associated with multiple features of PDAC progression, including hypoxia-related metabolic programs, tumor growth, and suppression of anti-tumor immunity. CD73 may therefore represent a biologically relevant biomarker and a potential therapeutic target in PDAC. - Source: PubMed
Publication date: 2026/07/27
Katsuta ErikoBurma Aarohan MukherjeeNakagawa EitoOh KenDai TaoDasgupta SubhamoyTakabe KazuakiBan Daisuke - Thyroid hormone (TH) is critical for a normal development of the nervous system and the maintenance of adult CNS functions. As a prerequisite of its cellular action, TH is taken up across CNS barriers and further into target cells by specialized transporters such as the monocarboxylate transporter 8 (MCT8). MCT8 mutations result in a severe form of psychomotor retardation that is accompanied by a prominent neuromotor component. Despite its central involvement in the relay of motor commands and somatosensation, potential contributions of spinal cord abnormalities to the MCT8 phenotype are elusive. In mice, a MCT8 deficiency-like phenotype can be induced by the combined deletion of Mct8 and the T4-specific organic anion transporting polypeptide 1c1 (Oatp1c1). Here, we first studied the expression pattern of Mct8 and Oatp1c1 in adult murine spinal cord sections by in situ hybridization and immunofluorescence. We detected Mct8 expression in endothelial cells and motoneurons, while Oatp1c1 was found in the endothelium and glia cells, thus resembling their pattern in the brain. Global absence of Mct8/Oatp1c1 results in reduced TH concentrations and affected TH signaling in the spinal cord in adult female mice. Immunofluorescence analyses and RNA sequencing pointed to unaltered myelination and cholinergic neurotransmission in Mct8/Oatp1c1 deficiency, whereas genes involved in sensory processing appeared differentially regulated. Finally, we demonstrated increased thermal sensitivity in the tail immersion test in adult female Mct8/Oatp1c1 deficient mice. Together, our results underscore a critical role of Mct8/Oatp1c1-mediated TH signaling for proper spinal cord function. - Source: PubMed
Publication date: 2026/08/10
Alcaide-Martin AndreaBudeus BettinaBauer ReinhardBoelen AnitaSchwaninger MarkusFührer DagmarHeuer HeikeMayerl Steffen