Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Lorenzo Galluzzi, Ilio Vitale, Laura Senovilla, Ken André Olaussen, Guillaume Pinna, Tobias Eisenberg, Aïcha Goubar, Isabelle Martins, Judith Michels, Gueorgui Kratassiouk, Didac Carmona-Gutierrez, Marie Scoazec, Erika Vacchelli, Frederic Schlemmer, Oliver Kepp, Shensi Shen, Maximilien Tailler, Mireia Niso-Santano, Eugenia Morselli, Alfredo CriolloSandy Adjemian, Mohamed Jemaà, Kariman Chaba, Claire Pailleret, Mickaël Michaud, Federico Pietrocola, Nicolas Tajeddine, Thibault de La Motte Rouge, Natalia Araujo, Nadya Morozova, Thomas Robert, Hugues Ripoche, Frederic Commo, Benjamin Besse, Pierre Validire, Pierre Fouret, Angélique Robin, Nicolas Dorvault, Philippe Girard, Sébastien Gouy, Patricia Pautier, Nora Jägemann, Ann Christin Nickel, Sabrina Marsili, Caroline Paccard, Nicolas Servant, Philippe Hupé, Carmen Behrens, Parviz Behnam-Motlagh, Kimitoshi Kohno, Isabelle Cremer, Diane Damotte, Marco Alifano, Øivind Midttun, Per Magne Ueland, Vladimir Lazar, Philippe Dessen, Hans Zischka, Etienne Chatelut, Maria Castedo, Frank Madeo, Emmanuel Barillot, Juergen Thomale, Ignacio Ivan Wistuba, Catherine Sautès-Fridman, Laurence Zitvogel, Jean Charles Soria, Annick Harel-Bellan, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)257-269
Number of pages13
JournalCell Reports
Volume2
Issue number2
DOIs
Publication statusPublished - Aug 30 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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