Luminal Iron Levels Govern Intestinal Tumorigenesis after Apc Loss In Vivo

Radulescu, Sorina, Brookes, Matthew J., Salgueiro, Pedro, Ridgway, Rachel A., McGhee, Ewan, Anderson, Kurt, Ford, Samuel J., Stones, Daniel H. ORCID: 0000-0002-8981-7943, Iqbal, Tariq H., Tselepis, Chris and Sansom, Owen J. (2012) Luminal Iron Levels Govern Intestinal Tumorigenesis after Apc Loss In Vivo. Cell Reports, 2 (2). pp. 270-282. doi:10.1016/j.celrep.2012.07.003

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Abstract

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.

Item Type:	Article
Article Type:	Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Daniel Stones
Date Deposited:	09 Oct 2018 08:38
Last Modified:	31 Aug 2023 08:59
URI:	https://eprints.glos.ac.uk/id/eprint/6060

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