Résumé
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.
langue originale | Anglais |
---|---|
Pages (de - à) | 257-269 |
Nombre de pages | 13 |
journal | Cell Reports |
Volume | 2 |
Numéro de publication | 2 |
Les DOIs | |
état | Publié - 30 août 2012 |
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Dans: Cell Reports, Vol 2, Numéro 2, 30.08.2012, p. 257-269.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
TY - JOUR
T1 - Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
AU - Galluzzi, Lorenzo
AU - Vitale, Ilio
AU - Senovilla, Laura
AU - Olaussen, Ken André
AU - Pinna, Guillaume
AU - Eisenberg, Tobias
AU - Goubar, Aïcha
AU - Martins, Isabelle
AU - Michels, Judith
AU - Kratassiouk, Gueorgui
AU - Carmona-Gutierrez, Didac
AU - Scoazec, Marie
AU - Vacchelli, Erika
AU - Schlemmer, Frederic
AU - Kepp, Oliver
AU - Shen, Shensi
AU - Tailler, Maximilien
AU - Niso-Santano, Mireia
AU - Morselli, Eugenia
AU - Criollo, Alfredo
AU - Adjemian, Sandy
AU - Jemaà, Mohamed
AU - Chaba, Kariman
AU - Pailleret, Claire
AU - Michaud, Mickaël
AU - Pietrocola, Federico
AU - Tajeddine, Nicolas
AU - de La Motte Rouge, Thibault
AU - Araujo, Natalia
AU - Morozova, Nadya
AU - Robert, Thomas
AU - Ripoche, Hugues
AU - Commo, Frederic
AU - Besse, Benjamin
AU - Validire, Pierre
AU - Fouret, Pierre
AU - Robin, Angélique
AU - Dorvault, Nicolas
AU - Girard, Philippe
AU - Gouy, Sébastien
AU - Pautier, Patricia
AU - Jägemann, Nora
AU - Nickel, Ann Christin
AU - Marsili, Sabrina
AU - Paccard, Caroline
AU - Servant, Nicolas
AU - Hupé, Philippe
AU - Behrens, Carmen
AU - Behnam-Motlagh, Parviz
AU - Kohno, Kimitoshi
AU - Cremer, Isabelle
AU - Damotte, Diane
AU - Alifano, Marco
AU - Midttun, Øivind
AU - Ueland, Per Magne
AU - Lazar, Vladimir
AU - Dessen, Philippe
AU - Zischka, Hans
AU - Chatelut, Etienne
AU - Castedo, Maria
AU - Madeo, Frank
AU - Barillot, Emmanuel
AU - Thomale, Juergen
AU - Wistuba, Ignacio Ivan
AU - Sautès-Fridman, Catherine
AU - Zitvogel, Laurence
AU - Soria, Jean Charles
AU - Harel-Bellan, Annick
AU - Kroemer, Guido
N1 - Funding Information: Dr. Fabienne Dufour is thanked for her assistance in tissue and clinical data collection. L.G., T.E., and S.S. are funded by Apo-Sys. D.C.G. receives a Lypotoxicity grant from the Austrian FWF. M.N-S. is funded by Junta de Extremadura (Spain). F.M. is grateful to the Austrian FWF (grants LIPOTOX, P23490-B12, P24381-B20, DK MCD W 1226-B18) and to the European Commission (grant Apo-Sys). A.H.B. received financial support from the Association pour la Recherche sur le Cancer (ARC). G.K. is supported by the Ligue Nationale contre le Cancer (Equipe labellisée), Agence Nationale pour la Recherche (ANR), European Commission (Active p53, Apo-Sys, Artforce, ChemoRes, ApopTrain), Fondation pour la Recherche Médicale (FRM), Institut National du Cancer (INCa), Cancéropôle Ile-de-France, AXA Research Fund, and the Labex Immuno-Oncology.
PY - 2012/8/30
Y1 - 2012/8/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865704717&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2012.06.017
DO - 10.1016/j.celrep.2012.06.017
M3 - Article
C2 - 22854025
AN - SCOPUS:84865704717
SN - 2639-1856
VL - 2
SP - 257
EP - 269
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -