{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:03:03Z","timestamp":1790229783459,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA269811"],"award-info":[{"award-number":["R01CA269811"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"HHS | NIH | National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R21EB027979"],"award-info":[{"award-number":["R21EB027979"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018095","name":"VT | Virginia-Maryland College of Veterinary Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011501","name":"VT | Institute for Critical Technologies and Applied Science, Virginia Tech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA274439"],"award-info":[{"award-number":["R01CA274439"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2212\/\u2212 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\u2013mesenchymal 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\u2013mesenchymal 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2200834","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:26:33Z","timestamp":1698845193000},"page":"1844-1857","source":"Crossref","is-referenced-by-count":5,"title":["Cellular Context Dictates the Suppression or Augmentation of Triple-Negative Mammary Tumor Metastasis by NLRX1"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6687-6476","authenticated-orcid":false,"given":"Margaret A","family":"Nagai-Singer","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-728X","authenticated-orcid":false,"given":"Mackenzie K","family":"Woolls","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0433-3390","authenticated-orcid":false,"given":"Katerina","family":"Leedy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8561-8288","authenticated-orcid":false,"given":"Alissa","family":"Hendricks-Wenger","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biology, Medicine and Health, Virginia Tech , Roanoke, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-6189","authenticated-orcid":false,"given":"Rebecca M","family":"Brock","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biology, Medicine and Health, Virginia Tech , Roanoke, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-3969","authenticated-orcid":false,"given":"Sheryl","family":"Coutermarsh-Ott","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4888-5915","authenticated-orcid":false,"given":"Tamalika","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-7728","authenticated-orcid":false,"given":"Holly A","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-8499","authenticated-orcid":false,"given":"Khan M","family":"Imran","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biology, Medicine and Health, Virginia Tech , Roanoke, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juselyn D","family":"Tupik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8323-627X","authenticated-orcid":false,"given":"Endia J","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Postbaccalaureate Research Education Program, Virginia Tech , Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-313X","authenticated-orcid":false,"given":"David A","family":"Brown","sequence":"additional","affiliation":[{"name":"Stealth BioTherapeutics , Needham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-5250","authenticated-orcid":false,"given":"Irving C","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech , Blacksburg, 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