Unknown,Transcriptomics,Genomics,Proteomics

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Critical role for the DNA receptor AIM2 in stem-cell proliferation and cancer

ABSTRACT: Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune receptor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators were largely intact in Aim2-deficient mice, however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with wild-type healthy mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer. We used microarrays to compare the transcriptome Aim2 deficent mice to wild type mice in colon tumor and colitis samples. Here were 12 mice in total, 3 for each genotype and tissue combination.

ORGANISM(S): Mus musculus

SUBMITTER: David Finkelstein

PROVIDER: E-GEOD-69436 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer.

Man Si Ming SM Zhu Qifan Q Zhu Liqin L Liu Zhiping Z Karki Rajendra R Malik Ankit A Sharma Deepika D Li Liyuan L Malireddi R K Subbarao RK Gurung Prajwal P Neale Geoffrey G Olsen Scott R SR Carter Robert A RA McGoldrick Daniel J DJ Wu Gang G Finkelstein David D Vogel Peter P Gilbertson Richard J RJ Kanneganti Thirumala-Devi TD

Cell 20150618 1

Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled p ...[more]

PMID: 26095253

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Dataset Information

Critical role for the DNA receptor AIM2 in stem-cell proliferation and cancer

Publications

Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer.

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