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However, its expression in adults is limited. Similar to other developmental transcription factors, NFIX has been found to be altered in tumors, often promoting pro-tumorigenic functions, such as leading to proliferation, differentiation, and migration. However, some studies suggest that NFIX can also have a tumor suppressor role, indicating a complex and cancer-type dependent role of NFIX. This complexity may be linked to the multiple processes at play in regulating NFIX, which include transcriptional, post-transcriptional, and post-translational processes. Moreover, other features of NFIX, including its ability to interact with different NFI members to form homodimers or heterodimers, therefore allowing the transcription of different target genes, and its ability to sense oxidative stress, can also modulate its function. In this review, we examine different aspects of NFIX regulation, first in development and then in cancer, highlighting the important role of NFIX in oxidative stress and cell fate regulation in tumors. Moreover, we propose different mechanisms through which oxidative stress regulates NFIX transcription and function, underlining NFIX as a key factor for tumorigenesis.<\/jats:p>","DOI":"10.3390\/ijms24054293","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:32:17Z","timestamp":1677036737000},"page":"4293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-3157","authenticated-orcid":false,"given":"Vanessa","family":"Ribeiro","sequence":"first","affiliation":[{"name":"cE3c-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Susana G.","family":"Martins","sequence":"additional","affiliation":[{"name":"cE3c-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Ana Sofia","family":"Lopes","sequence":"additional","affiliation":[{"name":"cE3c-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"},{"name":"Centro Hospitalar de Lisboa Ocidental (CHLO), 1449-005 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9018-3431","authenticated-orcid":false,"given":"S\u00f3lveig","family":"Thorsteinsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"cE3c-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Rita","family":"Zilh\u00e3o","sequence":"additional","affiliation":[{"name":"cE3c-CHANGE, Department of Plant Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-1163","authenticated-orcid":false,"given":"Ana Rita","family":"Carlos","sequence":"additional","affiliation":[{"name":"cE3c-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0378-1119(00)00140-2","article-title":"Roles of the NFI\/CTF gene family in transcription and development","volume":"249","author":"Gronostajski","year":"2000","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tcb.2018.09.003","article-title":"Nuclear factor one X in development and disease","volume":"29","author":"Piper","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1006\/geno.1995.1107","article-title":"Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by fish","volume":"28","author":"Qian","year":"1995","journal-title":"Genomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/0014-5793(94)00585-0","article-title":"Transcription factor nuclear factor I proteins form stable homo- and heterodimers","volume":"348","author":"Kruse","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_5","first-page":"1","article-title":"Human transcription factor protein interaction networks","volume":"13","author":"Kinnunen","year":"2022","journal-title":"Nat. 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