Inflammation-driven carcinogenesis is mediated through STING

Jeonghyun Ahn, Tianli Xia, Hiroyasu Konno, Keiko Konno, Phillip Ruiz, Glen N Barber

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by mechanisms that are not well understood. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), cisplatin and etoposide induce nuclear DNA leakage into the cytosol that intrinsically activates stimulator of interferon genes (STING)-dependent cytokine production. Inflammatory cytokine levels are subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild-type mice adoptively transferred with STING-/- bone marrow, are almost completely resistant to DMBA-induced skin carcinogenesis compared with their wild-type counterparts. Our data establish a role for STING in the control of cancer, shed significant insight into the causes of inflammation-driven carcinogenesis and may provide a basis for therapeutic strategies to help prevent malignant disease.

Original languageEnglish
Article number5166
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

Fingerprint

interferon
genes
Interferons
Carcinogenesis
Genes
Inflammation
9,10-Dimethyl-1,2-benzanthracene
mice
Cytokines
purging
Purging
bone marrow
Etoposide
Phagocytes
anthracene
stimulation
Cytosol
Cisplatin
Skin
Bone

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Inflammation-driven carcinogenesis is mediated through STING. / Ahn, Jeonghyun; Xia, Tianli; Konno, Hiroyasu; Konno, Keiko; Ruiz, Phillip; Barber, Glen N.

In: Nature Communications, Vol. 5, 5166, 2014.

Research output: Contribution to journalArticle

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