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 Criollo; Sandy 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

doi:10.1016/j.celrep.2012.06.017

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 journal › Article › peer-review

89 Scopus citations

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 language	English (US)
Pages (from-to)	257-269
Number of pages	13
Journal	Cell Reports
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2012.06.017
State	Published - Aug 30 2012

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2012.06.017

Cite this

Galluzzi, L., Vitale, I., Senovilla, L., Olaussen, K. A., Pinna, G., Eisenberg, T., Goubar, A., Martins, I., Michels, J., Kratassiouk, G., Carmona-Gutierrez, D., Scoazec, M., Vacchelli, E., Schlemmer, F., Kepp, O., Shen, S., Tailler, M., Niso-Santano, M., Morselli, E., ... Kroemer, G. (2012). Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer. Cell Reports, 2(2), 257-269. https://doi.org/10.1016/j.celrep.2012.06.017

Galluzzi, L, Vitale, I, Senovilla, L, Olaussen, KA, Pinna, G, Eisenberg, T, Goubar, A, Martins, I, Michels, J, Kratassiouk, G, Carmona-Gutierrez, D, Scoazec, M, Vacchelli, E, Schlemmer, F, Kepp, O, Shen, S, Tailler, M, Niso-Santano, M, Morselli, E, Criollo, A, Adjemian, S, Jemaà, M, Chaba, K, Pailleret, C, Michaud, M, Pietrocola, F, Tajeddine, N, de La Motte Rouge, T, Araujo, N, Morozova, N, Robert, T, Ripoche, H, Commo, F, Besse, B, Validire, P, Fouret, P, Robin, A, Dorvault, N, Girard, P, Gouy, S, Pautier, P, Jägemann, N, Nickel, AC, Marsili, S, Paccard, C, Servant, N, Hupé, P, Behrens, C, Behnam-Motlagh, P, Kohno, K, Cremer, I, Damotte, D, Alifano, M, Midttun, Ø, Ueland, PM, Lazar, V, Dessen, P, Zischka, H, Chatelut, E, Castedo, M, Madeo, F, Barillot, E, Thomale, J, Wistuba, II, Sautès-Fridman, C, Zitvogel, L, Soria, JC, Harel-Bellan, A & Kroemer, G 2012, 'Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer', Cell Reports, vol. 2, no. 2, pp. 257-269. https://doi.org/10.1016/j.celrep.2012.06.017

@article{069fd0941fb5401498e710b894613914,

title = "Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer",

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.",

author = "Lorenzo Galluzzi and Ilio Vitale and Laura Senovilla and Olaussen, {Ken Andr{\'e}} and Guillaume Pinna and Tobias Eisenberg and A{\"i}cha Goubar and Isabelle Martins and Judith Michels and Gueorgui Kratassiouk and Didac Carmona-Gutierrez and Marie Scoazec and Erika Vacchelli and Frederic Schlemmer and Oliver Kepp and Shensi Shen and Maximilien Tailler and Mireia Niso-Santano and Eugenia Morselli and Alfredo Criollo and Sandy Adjemian and Mohamed Jema{\`a} and Kariman Chaba and Claire Pailleret and Micka{\"e}l Michaud and Federico Pietrocola and Nicolas Tajeddine and {de La Motte Rouge}, Thibault and Natalia Araujo and Nadya Morozova and Thomas Robert and Hugues Ripoche and Frederic Commo and Benjamin Besse and Pierre Validire and Pierre Fouret and Ang{\'e}lique Robin and Nicolas Dorvault and Philippe Girard and S{\'e}bastien Gouy and Patricia Pautier and Nora J{\"a}gemann and Nickel, {Ann Christin} and Sabrina Marsili and Caroline Paccard and Nicolas Servant and Philippe Hup{\'e} and Carmen Behrens and Parviz Behnam-Motlagh and Kimitoshi Kohno and Isabelle Cremer and Diane Damotte and Marco Alifano and {\O}ivind Midttun and Ueland, {Per Magne} and Vladimir Lazar and Philippe Dessen and Hans Zischka and Etienne Chatelut and Maria Castedo and Frank Madeo and Emmanuel Barillot and Juergen Thomale and Wistuba, {Ignacio Ivan} and Catherine Saut{\`e}s-Fridman and Laurence Zitvogel and Soria, {Jean Charles} and Annick Harel-Bellan and Guido Kroemer",

note = "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 labellis{\'e}e), Agence Nationale pour la Recherche (ANR), European Commission (Active p53, Apo-Sys, Artforce, ChemoRes, ApopTrain), Fondation pour la Recherche M{\'e}dicale (FRM), Institut National du Cancer (INCa), Canc{\'e}rop{\^o}le Ile-de-France, AXA Research Fund, and the Labex Immuno-Oncology. ",

year = "2012",

month = aug,

day = "30",

doi = "10.1016/j.celrep.2012.06.017",

language = "English (US)",

volume = "2",

pages = "257--269",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "2",

}

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

UR - http://www.scopus.com/inward/citedby.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 - 2211-1247

VL - 2

SP - 257

EP - 269

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -

Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this