Non-cell-autonomous cancer progression from chromosomal instability.

ABSTRACT: Chromosomal instability (CIN) is a driver of cancer metastasis^1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signal

SUBMITTER: Li J 

PROVIDER: S-EPMC10468402 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature