Deoxysphingolipids activate cGAS-STING in colon cancer cells and enhance tumor immunity
Saha, S.; Velazquez, F. N.; Dehpanah, F.; Mao, C.; Montrose, D. C.
Show abstract
Deoxysphingolipids (deoxySLs) are a class of non-canonical sphingolipids that can adversely impact mitochondrial function. Mitochondrial disruption can activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING1) pathway, and in turn, promote antitumor immunity. Here, we investigated whether inducing deoxySL accumulation in colon cancer cells drives immune-specific, antitumor effects. We show that depleting serine increased deoxySLs and enhanced immune cell infiltration in colon tumors, in parallel with suppressing tumor growth. Elevating tumor deoxySL levels through mutation of SPT in cells and feeding a high alanine diet to mice exerted similar effects, including immune-mediated tumor growth suppression. Work conducted in multiple in vitro systems identified deoxySLs as key triggers of cGAS-STING1 activation, an effect mediated by mitochondrial release of double-stranded DNA resulting from mitochondrial stress. Collectively, these findings provide the first evidence that deoxySLs can drive antitumor immunity and identify a previously unrecognized metabolic strategy for cancer therapy.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Early neutrophilia marked by aerobic glycolysis sustains host metabolism and delays cancer cachexia 96%
- Histone deacetylase inhibitor induces acetyl-CoA depletion leading to lethal metabolic stress in RAS-pathway activated cells 95%
- Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines 94%
Similar papers in this journal
- Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy 95%
- The Cancer Testis Antigen Testis Specific Serine Kinase 6 (TSSK6) is abnormally expressed in colorectal cancer and promotes oncogenic behaviors 95%
- A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells 95%
Similar papers in this journal
- Targeting aggressive B-cell lymphomas through pharmacological activation of the mitochondrial protease OMA1 96%
- Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and CD155/TIGIT Pathway 95%
- Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer 95%
Similar papers in this journal
- The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival 96%
- Mitochondrial structure and function adaptation in residual triple negative breast cancer cells surviving chemotherapy treatment 95%
- Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+ T cells to suppress anti-tumor immunity 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.