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Carcinoma-astrocyte gap junctions promote brain metastasis by cytosolic dsDNA response transfer

GSE79256 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2017/02/09 Platform GPL11154
Summary
Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in brain metastasis. Cancer cells assemble of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Cx43 in cancer cells support brain metastatic colonization. We employ translating ribosome affinity purification (TRAP) to isolate translating mRNA from cancer cells in mixed asrtocyte co-cultures to determine the mechanism behind this Cx43-mediated brain metastatic growth. Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells employ these channels to transfer the cytosolic dsDNA response messenger cGAMP to astrocytes, activating the cGAS-STING pathway and production of inflammatory cytokines IFNα and TNFα. As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, which support tumour growth and chemoresistance.
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Also filed as BioProject PRJNA315285 and SRA study SRP071806. Searching any of these in the dataset finder brings you back here.

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