Abstract
Recent implication of chromosomal instability (CIN) in metastatic cancer cells has pointed to the frequency of chromosome missegregation as a key difference between primary and metastatic tumors. Understanding the cellular response therefore aids development of treatments to prevent metastasis. Chromosome missegregation creates micronuclei of double stranded DNA (dsDNA) fragments that are prone to rupture in the cytoplasm. The cGAS‐STING pathway responds to cytosolic dsDNA by activating inflammatory response pathways, a reaction useful to protect against viruses. Dimerization of cGAS, induced by dsDNA binding, catalyzes synthesis of cyclic GAMP (cGAMP) from ATP and GTP. Activation of cGAS results in upregulation of IFN‐β and NF‐κB stimulated immune response pathways. Cytosolic dsDNA associated with CIN has been proposed to induce cGAS‐STING mediated immune mimicry in cancer cells, allowing tumors to flourish in otherwise lethal environments. The Pingry School SMART Team, in conjunction with MSOE Center for BioMolecular Modeling, is using 3‐D modeling and printing technology to further examine the binding of cytosolic dsDNA to cGAS and the resultant production of the signaling molecule, cGAMP, by the enzyme. Stimulation of a cGAS‐STING inflammatory response due to CIN in cancer may contribute to the metastatic transition of primary tumor cells. The Pingry School SMART Team aims to utilize the cGAS structural model to better understand the role of this protein in responding to CIN and its link to metastasis through cytosolic dsDNA induced immune response.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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