Ask about this productRelated genes to: ENPP2 antibody
- Gene:
- ENPP2 NIH gene
- Name:
- ectonucleotide pyrophosphatase/phosphodiesterase 2
- Previous symbol:
- PDNP2
- Synonyms:
- ATX, PD-IALPHA
- Chromosome:
- 8q24.12
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-10
- Date modifiied:
- 2015-09-11
Related products to: ENPP2 antibody
Related articles to: ENPP2 antibody
- ENPP1 is emerging as a potential target for cancer immunotherapy due to its negatively regulatory effect on the STING pathway via hydrolysis of cGAMP. Herein, we report the identification and optimization of compound starting from hit compound . is a potent and selective ENPP1 inhibitor featuring a novel pyrrolo[1',2':1,6]pyrimido[5,4-]pyridazin-6(5)-one core scaffold. It exhibited substantial inhibitory activity against ENPP1 with an IC value of 9.5 nM, while showing weak inhibition against ENPP2/3. In the cGAMP-mediated STING pathway, this compound effectively enhanced the expression of downstream genes and promoted the phosphorylation of the relevant protein. Moreover, it displayed favorable pharmacokinetic properties and no evident cytotoxicity. In a 4T1 syngeneic mouse model, oral administration of compound demonstrated significant antitumor effects and enhanced the efficacy of both anti-PD-1 antibody and chemotherapy, with good tolerability. Collectively, these results highlight the potential of compound to potentiate STING-mediated antitumor immunity. - Source: PubMed
Publication date: 2026/05/26
Nong CuijieZhu MengyuanZheng WeilunYang JiachengWang HaidiLi ChuanghuiWen BojieLiu YuZhu XiaoyuZhu TaoXu YuHui HuiLai Yisheng - Hepatocellular carcinoma (HCC) shows substantial biological heterogeneity and commonly develops within an immunosuppressive microenvironment. Tumor-associated macrophages (TAMs), particularly M2-skewed subsets, are repeatedly associated with aggressive disease and may represent a biologically meaningful phenotype for biomarker development. Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) has been implicated in malignant behavior, but its linkage to TAM polarization and its potential as a laboratory-interpretable translational readout in HCC remain insufficiently clarified. ENPP2 expression was examined in paired HCC and adjacent tissues and referenced to public cohorts to provide clinical context. ENPP2 was overexpressed or silenced in HCC cells, followed by assays of proliferation, apoptosis, migration, and invasion. Macrophage polarization was evaluated using a noncontact Transwell coculture system with marker assessment and flow-cytometric readouts. Intracellular cyclic adenosine monophosphate (cAMP) was quantified, and forskolin was used to interrogate pathway involvement. Xenograft experiments were conducted to examine in vivo tumor growth. ENPP2 was upregulated in HCC and showed an association with unfavorable outcomes in public datasets. ENPP2 increased malignant phenotypes in HCC cells and shifted cocultured macrophages toward an M2-skewed state, whereas ENPP2 suppression produced the opposite pattern. ENPP2 modulation coincided with changes in intracellular cAMP signaling, and forskolin partially attenuated phenotypes observed after ENPP2 knockdown. These findings delineate a novel ENPP2/cAMP signaling axis that directly links tumor-intrinsic ENPP2 overexpression in HCC cells to the induction of M2-skewed TAM polarization, a mechanism that has not been previously characterized in HCC. This work not only identifies ENPP2 as a dual regulator of HCC cell malignancy and TAM polarization but also establishes cAMP as the critical intracellular mediator of this crosstalk, thereby strengthening the logical connection between these elements and advancing the understanding of HCC tumor-immune microenvironment interactions beyond existing literature. - Source: PubMed
Publication date: 2026/05/23
Chen ShiyiZheng JinliLong JianwuOu PengTong JianLin Fan - Choline is an essential nutrient required for the synthesis of key molecules, such as phosphatidylcholine, sphingomyelin, acetylcholine, and S-adenosylmethionine. Choline metabolism encompasses two phases, namely the postprandial and postabsorptive states. The former enables the digestion, absorption, distribution, and storage of choline derivatives after a meal, while the latter allows the cellular utilization of choline and the mobilization of stored choline-containing molecules during fasting. Understanding choline metabolism is fundamental to the study of lipid disorders such as steatohepatitis or atherosclerosis, as well as neurodegenerative diseases, including Alzheimer's disease, and inflammatory signaling pathways. Members of the alkaline phosphatase (AP) superfamily are prominent contributors to extracellular choline metabolism. Within this family, several APs and ectonucleotide pyrophosphatases/phosphodiesterases (ENPP) members are required for physiological choline metabolism. While intestinal alkaline phosphatase (IAP) and alkaline sphingomyelinase/ENPP7 both participate in the digestion of choline-containing derivatives in the gut during the postprandial phase, circulating ENPP2, ENPP6, and tissue-nonspecific alkaline phosphatase (TNAP) act during the postabsorptive phase to generate choline. In this review we first provide a comprehensive overview of choline metabolism and then describe how APs and ENPPs have functionally and structurally co-evolved to catalyze sequential reactions within this metabolic pathway. - Source: PubMed
Publication date: 2026/04/30
Lecornu FélixDrevet Mulard EvaBessueille LaurenceGerardin DaliaRautureau Gilles Jean PhilippeBallut LionelMagne David - Liver cirrhosis(LC) represents the end stage of chronic liver disease, yet reliable molecular markers remain limited. This study aimed to uncover potential diagnostic biomarkers and therapeutic targets for LC. - Source: PubMed
Publication date: 2026/03/14
Zhang KangChen TingJia ZhangyuZhao JunxiaHuang Na - Immune checkpoint inhibitors (ICI), including those that block PD-1/PD-L1, have revolutionized therapy for patients with non-small cell lung cancer. However, most patients demonstrate no clinical benefit or acquire resistance, even when tumors express PD-L1. This highlights the critical need to dissect tumor survival dependencies to overcome resistance. Using our Kras/p53-driven lung cancer models that demonstrate acquired or intrinsic resistance to ICI, we performed single-cell RNA sequencing and focused on predicted upstream regulators of differentially expressed genes in the malignant cell cluster of resistant tumors. We found that the micro-RNA miR-29 was downregulated in tumors with anti-PD-1 resistance, and that this was associated with significant upregulation of a multitude of miR-29 targets. Furthermore, we found expression of Enpp2/ATX, a gene encoding an immunosuppressive molecule, was modulated due to miR-29 loss. Re-expression of miR-29 in anti-PD-1 resistant models reduced ATX expression in tumor cells, diminished the fibrotic microenvironment, and increased CD8+ T-cell infiltration. These alterations promoted response to ICI in an anti-PD-1 resistant model by rewiring the tumor immune microenvironment, specifically through increased CD8+ T-cell infiltration, reduction of suppressive Ly6C+ monocytes, and a concomitant increase in pro-inflammatory macrophages. Additional analysis of publicly available RNA-sequencing data revealed tumors from lung adenocarcinoma patients with high miR-29 had increased CD8A and decreased CD14 expression, and broad enrichment in immunoregulatory pathways. Together, these data provide evidence that the miR-29 family regulates the tumor microenvironment, including antitumor immune-related pathways in lung cancer, through control of ATX among other target genes, with implications for ICI response. - Source: PubMed
Publication date: 2026/02/25
Horvat Natalie KSaint-Cloud MyritneyBint Abdullah Muslim RaihaanahTian YanhuaRodriguez B LeticiaHall Margaret ALabani-Motlagh AlirezaDiao LixiaWang JingLesinski Gregory BMoffitt Richard AGibbons Don LKonen Jessica M