{"doi":"10.4049/jimmunol.2200834","title":"Cellular Context Dictates the Suppression or Augmentation of Triple-Negative Mammary Tumor Metastasis by NLRX1","abstract":"Prior studies have defined multiple, but inconsistent, roles for the enigmatic pattern recognition receptor NLRX1 in regulating several cancer-associated biological functions. In this study, we explore the role of NLRX1 in the highly metastatic murine 4T1 mammary tumor model. We describe a functional dichotomy of NLRX1 between two different cellular contexts: expression in healthy host cells versus expression in the 4T1 tumor cells. Using Nlrx1-/- mice engrafted with 4T1 tumors, we demonstrate that NLRX1 functions as a tumor suppressor when expressed in the host cells. Specifically, NLRX1 in healthy host cells attenuates tumor growth and lung metastasis through suppressing characteristics of epithelial-mesenchymal transition and the lung metastatic niche. Conversely, we demonstrate that NLRX1 functions as a tumor promoter when expressed in 4T1 tumor cells using gain- and loss-of-function studies both in vitro and in vivo. Mechanistically, NLRX1 in the tumor cells augments 4T1 aggressiveness and metastasis through regulating epithelial-mesenchymal transition hallmarks, cell death, proliferation, migration, reactive oxygen species levels, and mitochondrial respiration. Collectively, we provide critical insight into NLRX1 function and establish a dichotomous role of NLRX1 in the 4T1 murine mammary carcinoma model that is dictated by cellular context.","journal":"The Journal of Immunology","year":2023,"id":375898,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1095940,"name":"Mackenzie K. Woolls","orcid":"0000-0003-0957-728X","position":1,"is_corresponding":false},{"id":1095941,"name":"Katerina Leedy","orcid":"0000-0003-0433-3390","position":2,"is_corresponding":false},{"id":642195,"name":"Alissa Hendricks-Wenger","orcid":"0000-0001-8561-8288","position":3,"is_corresponding":false},{"id":297445,"name":"Rebecca M. Brock","orcid":"0000-0003-4022-6189","position":4,"is_corresponding":false},{"id":350009,"name":"Sheryl Coutermarsh‐Ott","orcid":"0000-0001-7385-3969","position":5,"is_corresponding":false},{"id":1038258,"name":"Tamalika Paul","orcid":"0000-0002-4888-5915","position":6,"is_corresponding":false},{"id":628657,"name":"Holly A. Morrison","orcid":"0000-0001-7358-7728","position":7,"is_corresponding":false},{"id":691972,"name":"Khan Mohammad Imran","orcid":"0000-0003-0755-8499","position":8,"is_corresponding":false},{"id":951182,"name":"Juselyn D. Tupik","orcid":"0000-0003-4350-1553","position":9,"is_corresponding":false},{"id":1123607,"name":"Endia J. Fletcher","orcid":"0009-0003-8323-627X","position":10,"is_corresponding":false},{"id":1024163,"name":"David A. Brown","orcid":"0000-0001-5489-313X","position":11,"is_corresponding":false},{"id":297448,"name":"Irving C. Allen","orcid":"0000-0001-9573-5250","position":12,"is_corresponding":false},{"id":691971,"name":"Margaret A. Nagai-Singer","orcid":"0000-0001-6687-6476","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:16:23.381203Z","pmid":"37909827","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":[]}