{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T21:19:18Z","timestamp":1777756758016,"version":"3.51.4"},"reference-count":136,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006247","name":"Clinical and Transformation Research Project of Anhui Province","doi-asserted-by":"publisher","award":["202427b10020132"],"award-info":[{"award-number":["202427b10020132"]}],"id":[{"id":"10.13039\/501100006247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) remains a major cause of cancer-related death, and resistance to chemotherapy and radiotherapy continues to limit durable disease control. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has therefore emerged as a potential therapeutic strategy. However, models focused solely on glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) do not fully explain why CRC cells differ in their sensitivity to ferroptosis. In this review, we examine how ferroptosis in CRC is shaped by iron trafficking and selenium-dependent antioxidant defense. We first discuss the poly(rC)-binding proteins 1 and 2 (PCBP1\/2)-nuclear receptor coactivator 4 (NCOA4) axis, which regulates iron storage, trafficking, and ferritinophagy. We then review the AlkB homolog 8 (ALKBH8)-directed selenoprotein network, which supports the detoxification of lipid peroxides and maintenance of redox homeostasis. We next consider how these two systems intersect and how their interplay influences ferroptosis sensitivity. We also discuss why concurrent disruption of iron handling and selenium-dependent defense mechanisms may enhance therapeutic efficacy. Finally, we outline potential clinical applications, including combination strategies and biomarker development.<\/jats:p>","DOI":"10.3390\/ijms27093963","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:31:56Z","timestamp":1777465916000},"page":"3963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Fulin","family":"Tao","sequence":"first","affiliation":[{"name":"School of Medicine, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghui","family":"He","sequence":"additional","affiliation":[{"name":"National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Medicine, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, B., Yin, Y., Li, S., and Guo, X. 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