DNA-PK enables cGAS activation to promote cancer-associated inflammation

ABSTRACT: Cytosolic DNAs promote inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been thus suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that present undetectable cGAS levels to question whether alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex drives cGAS-independent inflammatory responses but that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment, a process that impairesd early tumorigenesis but co

ORGANISM(S): Danio rerio (zebrafish)

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PROVIDER: S-BIAD571 | bioimages |

REPOSITORIES: bioimages