The abstract is read at the publisher; the summary is JClub's.
Nuclear cGAS binding in human cells is recruited by AP-1 transcription factors and transcriptionally regulates cholesterol homeostasis, linking lipid control to tumor growth and therapy response.
- Why it matters: Nuclear cGAS is known mainly for restraining aberrant DNA sensing, but its physiological transcriptional roles and downstream links to lipid metabolism and treatment outcomes were unclear.
- What they did: The study built a genome-wide cGAS chromatin localization map in human cells using integrated CUT&RUN, RNA-seq, and metabolomics, then tested mechanisms involving LGALS3, ACAA2, PI(3,4,5)P3, and mTORC2/Akt signaling.
- The result: cGAS depletion increased cholesterol, PI(3,4,5)P3, and mTORC2/Akt activity, promoting xenografted tumor growth and resistance to DNA-damaging agents; in cGas-/- mice, hepatic cholesterol elevation was largely reversed by Akt inhibition but not STING.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.