Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation

Qifan Zhu; Si Ming Man; Prajwal Gurung; Zhiping Liu; Peter Vogel; Mohamed Lamkanfi; Thirumala-Devi Kanneganti

doi:10.4049/jimmunol.1402051

Back

Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation

Journal article

Peer reviewed

Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation

Qifan Zhu, Si Ming Man, Prajwal Gurung, Zhiping Liu, Peter Vogel, Mohamed Lamkanfi and Thirumala-Devi Kanneganti

The Journal of immunology (1950), Vol.193(10), pp.4779-4782

11/15/2014

DOI: 10.4049/jimmunol.1402051

PMCID: PMC4308418

PMID: 25320273

View Online

Abstract

Stimulator of IFN genes (STING) is a cytoplasmic innate immune sensor for cyclic dinucleotides that also serves a dual role as an adaptor molecule for a number of intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and autoimmune diseases, its physiological role in cancer is unknown. In this study, we show that STING-deficient mice are highly susceptible to colitis-associated colorectal cancer. Colons of STING-deficient mice exhibit significant intestinal damage and overt proliferation during early stages of tumorigenesis. Moreover, STING-deficient mice fail to restrict activation of the NF-κB- and STAT3-signaling pathways, which leads to increased levels of the proinflammatory cytokines IL-6 and KC. Therefore, our results identified an unexpected and important role for STING in mediating protection against colorectal tumorigenesis.

Colitis - genetics

Colorectal Neoplasms - genetics

Colitis - complications

NF-kappa B - immunology

Colitis - pathology

Colon - immunology

Chemokine CXCL1 - genetics

Membrane Proteins - deficiency

Colorectal Neoplasms - etiology

Colitis - immunology

STAT3 Transcription Factor - genetics

Interleukin-6 - genetics

Signal Transduction

Colon - pathology

Gene Expression Regulation - immunology

Membrane Proteins - genetics

Membrane Proteins - immunology

Mice, Knockout

Chemokine CXCL1 - immunology

Animals

Colorectal Neoplasms - immunology

NF-kappa B - genetics

Interleukin-6 - immunology

Mice

STAT3 Transcription Factor - immunology

Colorectal Neoplasms - pathology

Details

Title: Subtitle: Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation
Creators: Qifan Zhu - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163
Si Ming Man - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
Zhiping Liu - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
Peter Vogel - Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105
Mohamed Lamkanfi - Department of Medical Protein Research, Flemish Institute for Biotechnology, B-9000 Ghent, Belgium; and Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; Thirumala-Devi.Kanneganti@StJude.org
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.193(10), pp.4779-4782
DOI: 10.4049/jimmunol.1402051
PMID: 25320273
PMCID: PMC4308418
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI101935 / NIAID NIH HHS 281600 / European Research Council R01 CA163507 / NCI NIH HHS P30 CA021765 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS AI101935 / NIAID NIH HHS R37 AI101935 / NIAID NIH HHS CA163507 / NCI NIH HHS AR056296 / NIAMS NIH HHS
Language: English
Date published: 11/15/2014
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094358302771

Metrics

21 Record Views

136 Times Cited - Web of Science

See more details