Short-chain acyl-CoA dehydrogenase initiates mtDNA demethylation and leakage to fuel antitumor immunity in colorectal cancer - PubMed
5 hours ago
- #Metabolism
- #Immunotherapy
- #Colorectal Cancer
- ACADS deficiency in colorectal cancer cells promotes tumor progression by suppressing cGAS-STING signaling and creating an immunosuppressive tumor microenvironment.
- ACADS inhibits mito-DNMT1 to prevent mtDNA methylation, stabilizing mtDNA and reducing its leakage into the cytoplasm, which otherwise activates cGAS-STING.
- Modulating mito-DNMT1 can reverse the effects of ACADS deficiency, restoring antitumor immunity and inhibiting CRC growth.
- The drug hypericin was identified as an ACADS-binding compound that mimics ACADS overexpression, improving the immune TME and suppressing CRC.