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.
Open accessPublished version of a preprint
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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“Interestingly, cGAMP is also secreted from cancer cells via SLC19A1, which induces activation of the STING pathway in recipient cells.78, 79”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [78]
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“Using a genome wide CRISPR interference screen, SLC19A1, was identified as the first known major importer of cGAMP, which is taken up by host cells to activate intracellular STING pathway to elicit an antitumor immune response.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ritchie et al., 2019
In the citing paper
“Recently, a novel role of cGAMP as a soluble extracellular immunotransmitter produced and secreted by malignant cells has been identified.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ritchie et al., 2019
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Cites
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STING is a direct innate immune sensor of cyclic di-GMP
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Cited by
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The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293
Inflammatory microenvironment remodelling by tumour cells after radiotherapy
McLaughlin, M., Patin, E. C., Pedersen, M., Wilkins, A. C., Dillon, M. T., Melcher, A. A., & Harrington, K. J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0246-1 · Cited by 921
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)
- PMC
- PMC6711396
- 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
- bronze
- doi.org
- Licence
- 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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