2. Academic Validation
  3. Oleic Acid Dissolves cGAS-DNA Phase Separation to Inhibit Immune Surveillance

Oleic Acid Dissolves cGAS-DNA Phase Separation to Inhibit Immune Surveillance

  • Adv Sci (Weinh). 2023 Mar 22;e2206820. doi: 10.1002/advs.202206820.
Lina Wang 1,  Qiaoling Liu 1,  Na Wang 1,  Siru Li 1,  Wei Bian 1,  Zhen Sun 1,  Lulu Wang 2,  Li Wang 3,  Caigang Liu 4,  Chengli Song 1,  Quentin Liu 5,  Qingkai Yang 1
Affiliations

Affiliations

  • 1 Institute of Cancer Stem Cell, DaLian Medical University, Dalian, 116 044, P. R. China.
  • 2 School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116 024, P. R. China.
  • 3 CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116 023, P. R. China.
  • 4 Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110 004, P. R. China.
  • 5 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510 060, P. R. China.
PMID: 36950761 DOI: 10.1002/advs.202206820
Abstract

Phase separation (PS) is a fundamental principle in diverse life processes including immunosurveillance. Despite numerous studies on PS, little is known about its dissolution. Here, it is shown that oleic acid (OA) dissolves the Cyclic GMP-AMP Synthase (cGAS)-deoxyribonucleic acid (DNA) PS and inhibits immune surveillance of DNA. As solvent components control PS and metabolites are abundant cellular components, it is speculated that some metabolite(s) may dissolve PS. Metabolite-screening reveals that the cGAS-DNA condensates formed via PS are markedly dissolved by long-chain fatty acids, including OA. OA revokes intracellular cGAS-PS and DNA-induced activation. OA attenuates cGAS-mediated Antiviral and Anticancer immunosurveillance. These results link metabolism and immunity by dissolving PS, which may be targeted for therapeutic interventions.

Keywords

DNA-sensing; cGAS; cancer; phase separation.

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