1. Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
- Author
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Lorenzo Galluzzi, Frédéric Commo, Mohamed Jemaà, Mireia Niso-Santano, Catherine Sautès-Fridman, Nora Jägemann, Ilio Vitale, Per Magne Ueland, Marco Alifano, Diane Damotte, Nicolas Tajeddine, Benjamin Besse, Isabelle Cremer, Emmanuel Barillot, Philippe Dessen, Sandy Adjemian, Guido Kroemer, Laura Senovilla, Frank Madeo, Hugues Ripoche, Eugenia Morselli, Sebastien Gouy, Oliver Kepp, Juergen Thomale, Nicolas Servant, Aicha Goubar, Maria Castedo, Maximilien Tailler, Jean-Charles Soria, Pierre Fouret, Annick Harel-Bellan, Angélique Robin, Judith Michels, Ann Christin Nickel, Laurence Zitvogel, Patricia Pautier, Caroline Paccard, Claire Pailleret, Vladimir Lazar, Federico Pietrocola, Isabelle Martins, Hans Zischka, Gueorgui Kratassiouk, Natalia Araujo, Alfredo Criollo, Mickaël Michaud, Shensi Shen, Sabrina Marsili, Ken A. Olaussen, Nadya Morozova, Etienne Chatelut, Erika Vacchelli, Øivind Midttun, Kariman Chaba, Marie Scoazec, Thibault De La Motte Rouge, Carmen Behrens, Parviz Behnam-Motlagh, Frédéric Schlemmer, Guillaume Pinna, Pierre Validire, Ignacio I. Wistuba, Philippe Hupé, Kimitoshi Kohno, Nicolas Dorvault, Tobias Eisenberg, Philippe Girard, Thomas Robert, Didac Carmona-Gutierrez, UCL - SSS/IONS - Institute of NeuroScience, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
- Subjects
Adult ,Male ,Lung Neoplasms ,DNA damage ,Medizin ,Antineoplastic Agents ,Apoptosis ,Biology ,Disease-Free Survival ,Gene Expression Regulation, Enzymologic ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Animals ,Pyridoxal Kinase ,Lung cancer ,lcsh:QH301-705.5 ,Aged ,030304 developmental biology ,Aged, 80 and over ,Cisplatin ,0303 health sciences ,Middle Aged ,medicine.disease ,Pyridoxal kinase ,Vitamin B 6 ,Neoplasm Proteins ,3. Good health ,Gene Expression Regulation, Neoplastic ,Survival Rate ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Immunology ,Cancer cell ,Cancer research ,Biomarker (medicine) ,Female ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,medicine.drug - 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.
- Published
- 2012
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