The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid
Open accessAbstract
Vascular disrupting agents such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) represent a novel approach for cancer treatment. DMXAA has potent antitumor activity in mice and, despite significant preclinical promise, failed human clinical trials. The antitumor activity of DMXAA has been linked to its ability to induce type I IFNs in macrophages, although the molecular mechanisms involved are poorly understood. In this study, we identify stimulator of IFN gene (STING) as a direct receptor for DMXAA leading to TANK-binding kinase 1 and IFN regulatory factor 3 signaling. Remarkably, the ability to sense DMXAA was restricted to murine STING. Human STING failed to bind to or signal in response to DMXAA. Human STING also failed to signal in response to cyclic dinucleotides, conserved bacterial second messengers known to bind and activate murine STING signaling. Collectively, these findings detail an unexpected species-specific role for STING as a receptor for an anticancer drug and uncover important insights that may explain the failure of DMXAA in clinical trials for human cancer.
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Citations
Cites
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
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Self-citationSTING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
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Self-citationAIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
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Self-citationTriggering the Interferon Antiviral Response Through an IKK-Related Pathway
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Self-citationIFI16 is an innate immune sensor for intracellular DNA
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STING is a direct innate immune sensor of cyclic di-GMP
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Self-citationThe AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
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Cited by
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
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Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293
Metadata
- Authors
- Conlon, J., Burdette, D. L., Sharma, S., Bhat, N., Thompson, M., Jiang, Z., Rathinam, V. A. K., Monks, B., Jin, T., Xiao, T. S., Vogel, S. N., Vance, R. E., & Fitzgerald, K. A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-05
- Volume
- 190
- Issue
- 10
- Pages
- 5216-5225
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1866003637
- Cited by
- 434
- References
- 56
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid. https://app.cochat.ai/papers/10.4049/jimmunol.1300097
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- Conlon, J., Burdette, D. L., Sharma, S., Bhat, N., Thompson, M., Jiang, Z., Rathinam, V. A. K., Monks, B., Jin, T., Xiao, T. S., Vogel, S. N., Vance, R. E., & Fitzgerald, K. A. (2013). Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1300097
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
