• The role of CIN in cancer with cGAS/STING pathway
  • zhila shokrian,1,* Nahid shokrian,2 Danyal Farajnia Ric,3 Mobina Movahed Majd,4
    1. Student of research Committee,Medical University of Sarab
    2. Member Midwifery Scientific Association of Iran
    3. Student of research Committee Medical University of Sarab
    4. Student of research Committee,Medical University of Sarab


  • Introduction: Chromosomal instability (CIN) is a hallmark of human cancer and is associated with poor prognosis, metastasis, and treatment resistance.CIN in cancer cells has been reported to activate the cGAS-STING innate immune pathway through micronuclei formation. Thus, it affects tumor immunity and tumor progression. In addition to their well-characterized cellular mechanisms of action, their effect on chromosome segregation implicates the contribution of the cGAS-STING pathway leading to antitumor immunity. For this purpose, Zierhut et al. have shown that STING is an essential determinant of mitotic cell death in breast cancer cell lines treated with Taxol in vitro.cGAS can recognize dsDNA inside ruptured micronuclei that have fragile envelopes. This recognition leads to activation of downstream signaling, suggesting that CIN activates the cGAS/STING pathway mainly through micronuclei formation.
  • Methods: In this review article, we studied and analyzed the articles published from 2018 to 2022 using PubMed and Science Direct search engines and the desired keywords.
  • Results: Theoretically, the cGAS/STING pathway may affect chromosomal stability through actions during interphase that induces CIN during mitosis or direct effects on mitotic progression. These results indicate that STING activation regulates cGAS chromosomal stability. Furthermore, identifying a means to prevent tumor cell adaptation to cytosolic DNA will be critical to our ability to target a lethal characteristic of cancer for a therapeutic benefit.
  • Conclusion: Our findings provide the first evidence for the role of the cGAS/STING pathway in maintaining chromosomal homeostasis as a cell undergoes division. Our results suggest the first mechanism by which the cGAS–STING pathway directly regulates CIN without the involvement of the immune system and demonstrate that all components of the cGAS/STING/TBK1/IRF3 signaling pathway function together to maintain chromosomal stability. Given the widespread nature of CIN in human cancer, CIN-based therapies have the potential to profoundly impact clinical outcomes, including minimizing the onset of treatment resistance, treating advanced and metastatic disease, and enhancing systemic antitumor immunity.
  • Keywords: CIN,cGAS/STING,cancer