cGAS-STING/NF-κB signaling pathway

Overview

The cGAS-STING/NF-κB signaling pathway is an innate immune signaling axis that links detection of cytosolic DNA to inflammatory gene expression. In this pathway, cyclic GMP-AMP synthase (cGAS) senses aberrant DNA in the cytoplasm and activates STING, which then promotes downstream signaling events that can converge on NF-κB activation. NF-κB is a central transcription factor controlling the expression of proinflammatory cytokines, chemokines, and other mediators of immune and stress responses.

Biologically, this pathway is important in host defense, but excessive or chronic activation can contribute to inflammatory tissue injury, tumor-promoting inflammation, and neuroinflammatory processes. Because of this dual role, the cGAS-STING/NF-κB signaling pathway is increasingly studied as a therapeutic target in cancer, inflammatory disease, and disorders involving sterile inflammation. In the recent literature provided here, it appears in the context of inflammatory and vascular remodeling in triple-negative breast cancer, where pathway inhibition was associated with suppression of the inflammatory microenvironment.

Recent Publications Summary (latest 30 papers)

Recent studies have examined cGAS-STING/NF-κB signaling as a pro-inflammatory and pro-cellular senescence axis in diverse disease models, with several natural products and traditional formulations reported to suppress this pathway. In radiation-induced pulmonary fibrosis, emodin reduced collagen deposition, fibrotic markers, mitochondrial reactive oxygen species accumulation, and cytoplasmic mtDNA leakage, thereby inhibiting the mtDNA-cGAS-STING-NF-κB pathway and cellular senescence-associated secretory phenotype production in pulmonary epithelial cells 42405973Jul. In age-related bone loss, trimethylamine N-oxide (TMAO) induced MC3T3-E1 osteoblast cellular senescence and impaired osteogenic differentiation, while activation of cGAS-STING-NF-κB was linked to cytosolic DNA release; AAV9-mediated STING knockdown was used to probe this mechanism in vivo 42366244Jun. In psoriasis, Yinxie Granules were reported to specifically target STING/NF-κB blockade, reducing skin inflammation, immune-cell infiltration, and vasculopathy, with the study noting that STING/NF-κB was hyperactivated in severe disease. Babaodan was also described as suppressing inflammatory and vascular microenvironment changes in triple-negative breast cancer by inhibiting cGAS-STING/NF-κB signaling 41819510Mar.

Other publications in the set focused on NF-κB-centered inflammatory control without direct cGAS-STING targeting, but they reinforce the pathway’s broad relevance across inflammatory and degenerative conditions. Donkey milk exosomes alleviated dextran sulfate sodium-induced colitis by delivering anti-inflammatory miRNAs that directly targeted TLR4/NF-κB and NLRP3 signaling, improving barrier integrity and inflammatory readouts in inflammatory bowel disease models 42378030Jun. Phy-Blica-O reduced LPS-induced neuroinflammation through NF-κB pathway inhibition in microglia and mice 42361074Jun, while genistein from Thai fermented soybean attenuated osteoarthritis pathogenesis by dual inhibition of NF-κB and MAPK signaling and suppression of matrix metalloproteinases 42290531Jun. Additional studies reported NF-κB suppression in acute lung injury via MyD88 degradation by the molecular glue d21 42284437Jun, in traumatic brain injury via TLR4/MyD88/NF-κB and P300 HAT-related mechanisms with anacardic acid 41950807Apr, and in colitis via Perilla frutescens-derived nanovesicles that reprogrammed the immune microenvironment and reduced TLR4/MyD88/NF-κB activation 41875611Mar.

Several studies also linked NF-κB modulation to broader anti-inflammatory, anti-fibrotic, or anti-tumor effects in preclinical systems. 10-Shogaol from ginger inhibited inflammatory NF-κB signaling while also acting as a broad antiviral entry inhibitor against dengue and Zika viruses 42270434Jun. glutathione-conjugated gold nanoparticles reduced amyloid-β-induced neuroinflammation and tauopathy by inhibiting NF-κB and the NLRP3 inflammasome axis in a 3D human neural stem cell model 41997281Apr. In pancreatic cancer, loss or inhibition of the CDK1/Cyclin B1 complex restored NF-κB activity and increased GM-CSF production, promoting dendritic-cell recruitment and improving responses to PD-1 blockade 41921857Apr. Together, these publications position cGAS-STING/NF-κB and related NF-κB inflammatory signaling as recurring therapeutic nodes across fibrosis, osteoporosis, psoriasis, cancer, colitis, neuroinflammation, and acute injury models 42405973Jul42366244Jun41819510Mar.

What Changes, What Holds

1. cGAS-STING/NF-κB is being extended from inflammatory signaling to a broader senescence-linked injury program
NEW DIRECTION emodin’s effect in radiation-induced pulmonary fibrosis suggests the pathway is not only a driver of cytokine output but also part of a mtDNA/ROS-linked senescence and fibrotic remodeling loop. That broadens the baseline account, which already allowed for inflammatory tissue injury, by adding a more specific mechanistic link to cellular senescence and mitochondrial damage in lung epithelium 42405973Jul. The STING-centered osteoblast and psoriasis findings reinforce this same pro-inflammatory framing rather than overturning it 42366244Jun.

2. NF-κB remains a shared inflammatory node across unrelated disease models
REINFORCES These studies do not change the baseline mechanism; they show that NF-κB-centered control continues to recur in colitis, neuroinflammation, osteoarthritis, acute lung injury, traumatic brain injury, and colitis microenvironment remodeling. Because the overview already identifies NF-κB as a central transcription factor for proinflammatory mediators, this set mainly sharpens its breadth and therapeutic tractability rather than adding a new role 42378030Jun42361074Jun. The cGAS-STING arm is not directly implicated here, so the work supports the pathway’s downstream relevance without extending the core model.

3. NF-κB inhibition is still a recurring route to anti-inflammatory and anti-tumor effects, but one cancer result points in the opposite direction
REINFORCES Most of this paragraph strengthens the established view that dampening NF-κB can reduce neuroinflammation and tissue injury, consistent with the overview’s emphasis on inflammatory pathology. The pancreatic cancer finding is the main wrinkle: restoring NF-κB activity improved dendritic-cell recruitment and immunotherapy response, which shows that blanket NF-κB suppression is not universally desirable in cancer settings. That does not displace the baseline; it qualifies it by showing context dependence and a potential tradeoff in antitumor immunity 41997281Apr41921857Apr.

Overview update candidates: cGAS-STING/NF-κB may be worth adding as a senescence-linked mechanism in fibrosis; and NF-κB signaling may need a cautionary note that inhibition is not uniformly beneficial in cancer immunotherapy contexts.