Inflammation-driven carcinogenesis is mediated through STING

被引：361

作者：

Ahn, Jeonghyun ^{[1
,2
]}

Xia, Tianli ^{[1
,2
]}

Konno, Hiroyasu ^{[1
,2
]}

Konno, Keiko ^{[1
,2
]}

Ruiz, Phillip ^{[3
]}

Barber, Glen N. ^{[1
,2
]}

机构：

[1] Univ Miami, Sch Med, Dept Cell Biol, Miami, FL 33136 USA

[2] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[3] Univ Miami, Sch Med, Dept Surg, Miami, FL 33136 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

AUTOIMMUNE-DISEASE; NUCLEIC-ACIDS; CANCER; CELLS; SKIN; TREX1; IMMUNITY; DAMAGE; MICE;

D O I：

10.1038/ncomms6166

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：9

共 25 条

[1]

STING manifests self DNA-dependent inflammatory disease [J].