TBK1-Zyxin signaling mitigates antitumor immunity by mechanical control of tumor-associated macrophage residency

ABSTRACT: Mechanical control of cell residency, such as tumor-associated macrophages (TAMs), is a fundamental cellular and tissue physiology process. While innate immune sensing pathways such as cGAS-STING signaling and RLR-MAVS signaling impact both the pathogenesis and therapeutics of malignant diseases, their effects on cell residency and motility remain incompletely understood. Here, we uncovered a novel biological function by which TBK1, activated by cGAS-STING or RLR-MAVS signaling, directly phosphorylates and mobilizes Zyxin, a key regulator of actin dynamics. Under pathological conditions, TBK1-mediated Zyxin phosphorylation at the S143 residue in STING or MAVS signalosomes facilitates rapid recruitment of phospho-Zyxin to focal adhesions, a process independent of IRF3 and leads to subsequen

ORGANISM(S): Homo sapiens (human) Mus musculus (mouse)

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PROVIDER: S-BSST1517 | biostudies-other |

REPOSITORIES: biostudies-other