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Title : Cytoplasmic DNA And Metastasis
link : Cytoplasmic DNA And Metastasis

Cytoplasmic DNA And Metastasis

Chromosomal instability results in DNA in the cytoplasm, which is of course not normal, DNA being normally found only in the nucleus.  This misplaced cytoplasmic DNA triggers a pathway that simulates cell signaling that can promote metastasis.  This could in theory be targeted to inhibit metastasis (keep in mind that cancer mortality is for the most part due to metastasis).  Abstract:

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.

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