{"doi":"10.17615/9bxe-7132","title":"The Innate Immune Receptor NLRX1 Functions as a Tumor Suppressor by Reducing Colon Tumorigenesis and Key Tumor-Promoting Signals","abstract":"NOD-like receptor (NLR) proteins are intracellular innate immune sensors/receptors that regulate immunity. This work shows that NLRX1 serves as a tumor suppressor in colitis-associated cancer (CAC) and sporadic colon cancer by keeping key tumor promoting pathways in check. Nlrx1(-/-) mice were highly susceptible to CAC, showing increases in key cancer-promoting pathways including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and interleukin 6 (IL-6). The tumor-suppressive function of NLRX1 originated primarily from the non-hematopoietic compartment. This prompted an analysis of NLRX1 function in the Apc(min/+) genetic model of sporadic gastrointestinal cancer. NLRX1 attenuated Apc(min/+) colon tumorigenesis, cellular proliferation, NF-κB, MAPK, STAT3 activation, and IL-6 levels. Application of anti-interleukin 6 receptor (IL6R) antibody therapy reduced tumor burden, increased survival, and reduced STAT3 activation in Nlrx1(-/-)Apc(min/+) mice. As an important clinical correlate, human colon cancer samples expressed lower levels of NLRX1 than healthy controls in multiple patient cohorts. These data implicate anti-IL6R as a potential personalized therapy for colon cancers with reduced NLRX1.","journal":"Carolina Digital Repository (University of North Carolina at Chapel Hill)","year":2020,"id":135274,"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":0.9551,"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":592010,"name":"Zengshan Li","orcid":"0000-0002-3368-1434","position":1,"is_corresponding":false},{"id":225644,"name":"W. June Brickey","orcid":"0000-0002-6503-539X","position":2,"is_corresponding":false},{"id":526166,"name":"P. Kay Lund","orcid":null,"position":3,"is_corresponding":false},{"id":280045,"name":"A. Alicia Koblansky","orcid":null,"position":4,"is_corresponding":false},{"id":237266,"name":"Christian Jobin","orcid":"0000-0002-3733-1001","position":5,"is_corresponding":false},{"id":323161,"name":"Rongrong Liu","orcid":"0000-0001-7853-7762","position":6,"is_corresponding":false},{"id":558619,"name":"Shengli Ding","orcid":"0000-0003-4657-1506","position":7,"is_corresponding":false},{"id":105115,"name":"Stephanie A. Montgomery","orcid":"0000-0001-8012-5302","position":8,"is_corresponding":false},{"id":396625,"name":"Peizhen Hu","orcid":null,"position":9,"is_corresponding":false},{"id":531436,"name":"Justin E. Wilson","orcid":"0000-0002-2803-3280","position":10,"is_corresponding":false},{"id":225654,"name":"Jenny P.‐Y. Ting","orcid":"0000-0002-3282-419X","position":11,"is_corresponding":false},{"id":307737,"name":"Marcus Mühlbauer","orcid":"0000-0003-2453-8262","position":12,"is_corresponding":false},{"id":532318,"name":"Agnieszka D. Truax","orcid":null,"position":13,"is_corresponding":false},{"id":592640,"name":"Rita-Marie T. McFadden","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:31.787520Z","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":[]}