ArticleProceedings of the National Academy of Sciences of the United States of America2023
ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 55 citations in OpenAlex.
- ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.Cancer biology & therapy · 2026Article
- From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma.British journal of cancer · 2026Article
- SEVs-carried ENPP1 regulates DCs' activation and inhibits the formation of tertiary lymphoid structures in gastric cancer.Journal of gastroenterology · 2026Article
- TCR γδ cell-specific STAT5 gain of function induces a druggable chronic human immune dysregulation.Journal of human immunity · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Review
- Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response.bioRxiv : the preprint server for biology · 2026Article
- Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population.Biochemical genetics · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Mechanistic insights and therapeutic potential of targeting the cGAS-STING pathway in neurodegenerative diseases.Journal of neuroinflammation · 2026Review
- Next-Generation Artificial Intelligence Strategies for Mechanistic Cancer Target Discovery and Drug Development: A State-of-the-Art Review.International journal of molecular sciences · 2026Review
- The cGAS-STING pathway in cancer: friend or foe.Cell death & disease · 2026Review
- Soft-Drug-Inspired MnSTF Nano-Adjuvant for Safe and Synergistic cGAS-STING Activation in Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tanshinone IIA&Icaritin -MPs regulated vascular normalization and restored tumor-infiltrating T lymphocyte function to boost anti-PD-1 therapy in melanoma lung metastasis.Journal of nanobiotechnology · 2026Article
- Control of poorly immunogenic tumors with systemic STING agonist-loaded liposomes targeting cross-presenting dendritic cells.Clinical & translational immunology · 2026Article
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- The cGAS-STING pathway in pulmonary infectious and sterile inflammation: differences, connections, and therapeutic implications.Frontiers in immunology · 2026Review
- Bone marrow stromal cells enhance multiple myeloma cells proliferation through regulating LncRNA OVAAL/ENPP1 axis.Open life sciences · 2026Article
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14 authors at 3 institutions in 1 country.
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Abstract
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) expression correlates with poor prognosis in many cancers, and we previously discovered that ENPP1 is the dominant hydrolase of extracellular cGAMP: a cancer-cell-produced immunotransmitter that activates the anticancer stimulator of interferon genes (STING) pathway. However, ENPP1 has other catalytic activities and the molecular and cellular mechanisms contributing to its tumorigenic effects remain unclear. Here, using single-cell RNA-seq, we show that ENPP1 in both cancer and normal tissues drives primary breast tumor growth and metastasis by dampening extracellular 2'3'-cyclic-GMP-AMP (cGAMP)-STING-mediated antitumoral immunity. ENPP1 loss-of-function in both cancer cells and normal tissues slowed primary tumor growth and abolished metastasis. Selectively abolishing the cGAMP hydrolysis activity of ENPP1 phenocopied ENPP1 knockout in a STING-dependent manner, demonstrating that restoration of paracrine cGAMP-STING signaling is the dominant anti-cancer mechanism of ENPP1 inhibition. Finally,
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.