Cited by 335interferon and immune responsesPhosphodiesterase function and regulationAdenosine and Purinergic Signaling

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

SLC19A1 is an importer of the immunotransmitter cGAMP.

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Abstract

2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen, we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2'3'-bisphosphosphothioate-cyclic-di-AMP (2'3'-CDA S). These discoveries will provide insight into cGAMP's role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.

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Metadata

Authors
Ritchie, C., Cordova, A. F., Hess, G. T., Bassik, M. C., & Li, L.
Affiliations
  • Stanford University (US)
  • Stanford Medicine (US)
Corresponding author
Li, Lingyin
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-07
Volume
75
Issue
2
Pages
372-381.e5
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2952481556
Cited by
333
References
44
Citations by year
2026: 35 · 2025: 38 · 2024: 49 · 2023: 55 · 2022: 53 · 2021: 46 · 2020: 47 · 2019: 10
FWCI
15.75
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (5R00CA19089, DP2HD084069, DP2CA228044, 2T32GM007365, 5T32GM007276)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
SLC19A1, cGAMP, STING pathway, STING agonist, cancer immunotherapy, membrane transport, antitumor immunity
MeSH terms
STING Protein, Cell Membrane, Humans, Immunity, Innate, Membrane Proteins, Neoplasms, Nucleotides, Cyclic, Signal Transduction, Genome, Human, Cell Line, Tumor, Reduced Folate Carrier Protein, CRISPR-Cas Systems

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