AI Article Synopsis
- Self-DNA found in the cytosol of cancer cells can trigger immune responses against tumors, but how it gets there is unclear.
- The study identifies the role of MUS81 and PARP in creating cytosolic DNA in prostate cancer cells, revealing that DNA damage from MUS81 correlates with cancer progression stages.
- This cytosolic DNA activates the STING pathway, boosting immune responses and leading to the rejection of tumor cells, highlighting the tumor-suppressive function of MUS81 in alerting the immune system.
Article Abstract
Self-DNA is present in the cytosol of many cancer cells and can promote effective immune rejection of tumor cells, but the mechanisms leading to the presence of cytosolic DNA are unknown. Here, we report that the cleavage of genomic DNA by DNA structure-specific endonuclease MUS81 and PARP-dependent DNA repair pathways leads to the accumulation of cytosolic DNA in prostate cancer cells. The number of nuclear MUS81 foci and the amount of cytosolic dsDNA increased in tandem from hyperplasia to clinical stage II prostate cancers and decreased at stage III. Cytosolic DNA generated by MUS81 stimulated DNA sensor STING-dependent type I interferon (IFN) expression and promoted phagocytic and T cell responses, resulting in type I and II IFN-mediated rejection of prostate tumor cells via mechanisms that partly depended on macrophages. Our results demonstrate that the tumor suppressor MUS81 alerts the immune system to the presence of transformed host cells.
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| http://dx.doi.org/10.1016/j.immuni.2016.04.010 | DOI Listing |
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