Evidence map›Paper›PMID 26107252›Full record

ArticleNature medicine2015

Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt.

Justin E Wilson, Alex S Petrucelli, Liang Chen, A Alicia Koblansky, Agnieszka D Truax, Yoshitaka Oyama, Arlin B Rogers, W June Brickey, Yuli Wang, Monika Schneider and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers.

0numbers the graph read from it
0cells of the map it votes in
193citing papers in PubMed
13.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

193 citing papers in PubMed, 289 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

133 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 1 country.

Justin E Wilson1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Alex S Petrucelli1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Liang Chen1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
A Alicia Koblansky1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Agnieszka D Truax1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Yoshitaka Oyama1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Arlin B RogersDepartment of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA.
W June Brickey1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Yuli WangDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Monika SchneiderThe American Association of Immunologists, Bethesda, Maryland, USA.
Marcus Mühlbauer1] Department of Medicine, Division of Gastroenterology, University of Florida College of Medicine, Gainesville, Florida, USA. [2] Department of Infectious Diseases &Pathology, University of Florida College of Medicine, Gainesville, Florida, USA.
Wei-Chun Chou1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Brianne R BarkerDepartment of Biology, Drew University, Madison, New Jersey, USA.
Christian Jobin1] Department of Medicine, Division of Gastroenterology, University of Florida College of Medicine, Gainesville, Florida, USA. [2] Department of Infectious Diseases &Pathology, University of Florida College of Medicine, Gainesville, Florida, USA.
Nancy L AllbrittonDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Dale A Ramsden1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, USA.
Beckley K DavisDepartment of Biology, Franklin &Marshall College, Lancaster, Pennsylvania, USA.
Jenny P Y Ting1] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [3] Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
University of North Carolina at Chapel Hill · USUNC Lineberger Comprehensive Cancer CenterAmerican Association of Immunologists · USDrew University · USFlorida College · USFranklin & Marshall College · USTufts University · USUniversity of Florida · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Somatostatin analogues as countermeasures against intestinal radiation toxicityU19AI067798 · NIAID · DUKE UNIVERSITY · PI CHAO, NELSON J. · 2005 to 2024
$82.1M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEIKH, SHEHZAD Z. · 2013 to 2023
$17.9M
Molecular and Functional Analysis of NLR Family MembersR01AI029564 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jenny P Ting · 1991 to 2026
$6.0M
Resolution of Complex Breaks by Nonhomologous End JoiningR01CA084442 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2000 to 2019
$4.8M
Plexin-A1: Regulation by CIITA and Immunologic FunctionR37AI029564 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TING, JENNY P · 2008 to 2017
$3.8M
Colitis, Colon Cancer and the NLR FamilyR01CA156330 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TING, JENNY P · 2011 to 2019
$3.0M
Generation of a Gene-Targeted Human iPS Cell Library for Macular DegenerationR01EY024556 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ALLBRITTON, NANCY L. · 2014 to 2018
$2.9M
Nucleotide binding characteristics of disease associated mutant NOD2 proteinsR15DK098754 · NIDDK · FRANKLIN AND MARSHALL COLLEGE · PI DAVIS, BECKLEY K · 2014 to 2014
$246k
Interaction of Retinoid X Receptors and NOD-Like Receptors in Colon InflammationF32DK098916 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TRUAX, AGNIESZKA DOROTA · 2013 to 2015
$132k
NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA084442NCI NIH HHS R01 CA156330NCI NIH HHS R01-CA156330NCI NIH HHS T32 CA009156NEI NIH HHS R01 EY024556NIAID NIH HHS R01 AI029564NIAID NIH HHS R37 AI029564NIAID NIH HHS R37-AI029564NIAID NIH HHS U19 AI067798NIAID NIH HHS U19-AI067798NIDDK NIH HHS F32 DK088417NIDDK NIH HHS F32 DK098916NIDDK NIH HHS P01 DK094779NIDDK NIH HHS P30 DK034987NIDDK NIH HHS R15 DK098754PHS HHS NIDDK F32-K088417-01
6 · The paper itself

Abstract

The inflammasome activates caspase-1 and the release of interleukin-1β (IL-1β) and IL-18, and several inflammasomes protect against intestinal inflammation and colitis-associated colon cancer (CAC) in animal models. The absent in melanoma 2 (AIM2) inflammasome is activated by double-stranded DNA, and AIM2 expression is reduced in several types of cancer, but the mechanism by which AIM2 restricts tumor growth remains unclear. We found that Aim2-deficient mice had greater tumor load than Asc-deficient mice in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colorectal cancer. Tumor burden was also higher in Aim2(-/-)/Apc(Min/+) than in APC(Min/+) mice. The effects of AIM2 on CAC were independent of inflammasome activation and IL-1β and were primarily mediated by a non-bone marrow source of AIM2. In resting cells, AIM2 physically interacted with and limited activation of DNA-dependent protein kinase (DNA-PK), a PI3K-related family member that promotes Akt phosphorylation, whereas loss of AIM2 promoted DNA-PK-mediated Akt activation. AIM2 reduced Akt activation and tumor burden in colorectal cancer models, while an Akt inhibitor reduced tumor load in Aim2(-/-) mice. These findings suggest that Akt inhibitors could be used to treat AIM2-deficient human cancers.

Indexed as

AnimalsColitisColonic NeoplasmsDNA-Activated Protein KinaseDNA-Binding ProteinsFemaleHCT116 CellsHumansInflammasomesIntestinal PolypsMaleMiceMice, Inbred C57BLPhosphorylationProto-Oncogene Proteins c-aktAim2 protein, mouseDNA-Activated Protein KinaseDNA-Binding ProteinsInflammasomesProto-Oncogene Proteins c-akt

Identifiers

PMID26107252
PMCPMC4529369
OpenAlexW1805865584

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.