{"doi":"10.17615/pb22-wq66","title":"Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt","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−/−/ApcMin/+ than in APCMin/+ 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.","journal":"UNC Libraries","year":2020,"id":143883,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299129,"name":"Jenny P.‐Y. Ting","orcid":"0000-0002-7846-0395","position":1,"is_corresponding":false},{"id":448788,"name":"Dale A. Ramsden","orcid":"0000-0003-1575-4748","position":2,"is_corresponding":false},{"id":237266,"name":"Christian Jobin","orcid":"0000-0002-3733-1001","position":3,"is_corresponding":false},{"id":532318,"name":"Agnieszka D. Truax","orcid":null,"position":4,"is_corresponding":false},{"id":532317,"name":"W June Brickey","orcid":null,"position":5,"is_corresponding":false},{"id":531436,"name":"Justin E. Wilson","orcid":"0000-0002-2803-3280","position":6,"is_corresponding":false},{"id":531435,"name":"Wei‐Chun Chou","orcid":"0000-0003-3355-6921","position":7,"is_corresponding":false},{"id":595022,"name":"Brianne R. Barker","orcid":"0000-0001-6932-479X","position":8,"is_corresponding":false},{"id":225645,"name":"Liang Chen","orcid":"0000-0002-3605-8883","position":9,"is_corresponding":false},{"id":537996,"name":"Beckley K. Davis","orcid":"0000-0003-0673-8017","position":10,"is_corresponding":false},{"id":527928,"name":"Arlin B. Rogers","orcid":null,"position":11,"is_corresponding":false},{"id":284766,"name":"Nancy L. Allbritton","orcid":"0000-0002-9242-768X","position":12,"is_corresponding":false},{"id":612375,"name":"A Alicia Koblansky","orcid":null,"position":13,"is_corresponding":false},{"id":611950,"name":"Yuli Wang","orcid":"0009-0007-0706-1139","position":14,"is_corresponding":false},{"id":522209,"name":"Monika Schneider","orcid":"0000-0002-3937-4080","position":15,"is_corresponding":false},{"id":612376,"name":"Alex S Petrucelli","orcid":null,"position":16,"is_corresponding":false},{"id":307737,"name":"Marcus Mühlbauer","orcid":"0000-0003-2453-8262","position":17,"is_corresponding":false},{"id":612374,"name":"Yoshitaka Oyama","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}