Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo
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It is clear from epidemiological studies that excess iron is associated with increased risk of colorectal cancer; however, questions regarding the mechanism of how iron increases cancer risk, the source of the excess iron (circulating or luminal), and whether iron reduction represents a potential therapeutic option remain unanswered. In this study, we show that after Apc deletion, the cellular iron acquisition proteins TfR1 and DMT1 are rapidly induced. Conversely, restoration of APC reduces cellular iron due to repression of these proteins. To test the functional importance of these findings, we performed in vivo investigations of the impact of iron levels on intestinal tumorigenesis. Strikingly, depletion of luminal (but not systemic) iron strongly suppressed murine intestinal tumorigenesis, whereas increased luminal iron strongly promoted tumorigenesis. Taken together, our data definitively delineate iron as a potent modifier of intestinal tumorigenesis and have important implications for dietary iron supplementation in patients at high risk of colorectal cancer.
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Upregulation of the Tf/TfR iron acquisition pathway is found in a variety of cancers, including breast and colon.
“Upregulation of this highly conserved iron acquisition pathway is found in a variety of cancers, including breast and colon [90,91,92,93].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [93]
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- Authors
- Radulescu, S., Brookes, M. J., Salgueiro, P., Ridgway, R. A., McGhee, E., Anderson, K., Ford, S. J., Stones, D. H., Iqbal, T. H., Tselepis, C., & Sansom, O. J.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Cancer Research UK (GB)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 2
- Issue
- 2
- Pages
- 270-282
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2083484178
- Cited by
- 130
- References
- 44
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 12 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 10 · 2013: 9
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-12-06)
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Repository (University of Gloucestershire) (acceptedVersion)
- Research Repository (University of Gloucestershire) (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- Cancer Research UK (15565, 12481)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- intestinal tumorigenesis, APC loss, colorectal cancer, transferrin receptor 1, DMT1, iron acquisition, dietary iron supplementation, iron depletion
- MeSH terms
- Solute Carrier Family 11, Member 2, Animals, Cell Transformation, Neoplastic, Humans, Intestinal Mucosa, Intestines, Iron, Receptors, Transferrin, Colorectal Neoplasms, Gene Deletion, Mice, Knockout, Dietary Supplements, Adenomatous Polyposis Coli Protein, Cation Transport Proteins, Mice
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