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'-CDAS). These discoveries will provide insight into cGAMP's role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.
journal_name
Mol Celljournal_title
Molecular cellauthors
Ritchie C,Cordova AF,Hess GT,Bassik MC,Li Ldoi
10.1016/j.molcel.2019.05.006subject
Has Abstractpub_date
2019-07-25 00:00:00pages
372-381.e5issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(19)30359-4journal_volume
75pub_type
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