Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2012-08-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221112471200191X
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author 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
spellingShingle 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
Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
Cell Reports
author_facet 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
author_sort Lorenzo Galluzzi
title Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
title_short Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
title_full Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
title_fullStr Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
title_full_unstemmed Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer
title_sort prognostic impact of vitamin b6 metabolism in lung cancer
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2012-08-01
description Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.
url http://www.sciencedirect.com/science/article/pii/S221112471200191X
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spelling doaj-c962346fede94134a0ec7d5f7e6f4ffd2020-11-24T20:58:22ZengElsevierCell Reports2211-12472012-08-012225726910.1016/j.celrep.2012.06.017Prognostic Impact of Vitamin B6 Metabolism in Lung CancerLorenzo Galluzzi0Ilio Vitale1Laura Senovilla2Ken André Olaussen3Guillaume Pinna4Tobias Eisenberg5Aïcha Goubar6Isabelle Martins7Judith Michels8Gueorgui Kratassiouk9Didac Carmona-Gutierrez10Marie Scoazec11Erika Vacchelli12Frederic Schlemmer13Oliver Kepp14Shensi Shen15Maximilien Tailler16Mireia Niso-Santano17Eugenia Morselli18Alfredo Criollo19Sandy Adjemian20Mohamed Jemaà21Kariman Chaba22Claire Pailleret23Mickaël Michaud24Federico Pietrocola25Nicolas Tajeddine26Thibault de La Motte Rouge27Natalia Araujo28Nadya Morozova29Thomas Robert30Hugues Ripoche31Frederic Commo32Benjamin Besse33Pierre Validire34Pierre Fouret35Angélique Robin36Nicolas Dorvault37Philippe Girard38Sébastien Gouy39Patricia Pautier40Nora Jägemann41Ann-Christin Nickel42Sabrina Marsili43Caroline Paccard44Nicolas Servant45Philippe Hupé46Carmen Behrens47Parviz Behnam-Motlagh48Kimitoshi Kohno49Isabelle Cremer50Diane Damotte51Marco Alifano52Øivind Midttun53Per Magne Ueland54Vladimir Lazar55Philippe Dessen56Hans Zischka57Etienne Chatelut58Maria Castedo59Frank Madeo60Emmanuel Barillot61Juergen Thomale62Ignacio Ivan Wistuba63Catherine Sautès-Fridman64Laurence Zitvogel65Jean-Charles Soria66Annick Harel-Bellan67Guido Kroemer68INSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceUniversité Paris-Sud XI, PArI Platform, F-91191 Gif-sur-Yvette, FranceInstitute of Molecular Biosciences, University of Graz, A-8010 Graz, AustriaInstitut Gustave Roussy, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceUniversité Paris-Sud XI, PArI Platform, F-91191 Gif-sur-Yvette, FranceInstitute of Molecular Biosciences, University of Graz, A-8010 Graz, AustriaInstitut Gustave Roussy, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceINSERM, U848, F-94805 Villejuif, FranceService d’Oncologie Médicale, Groupe Hospitalier Pitié-Salpêtrière, F-75651 Paris, FranceUniversité Paris-Sud XI, PArI Platform, F-91191 Gif-sur-Yvette, FranceUniversité Paris-Sud XI, PArI Platform, F-91191 Gif-sur-Yvette, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceService d’Anatomie Pathologique, Institut Mutualiste Montsouris, F-75014 Paris, FranceINSERM, U985, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceDépartement Thoracique, Institut Mutualiste Montsouris, F-75014 Paris, FranceDepartment of Surgery, Institut Gustave Roussy, F-94805 Villejuif, FranceDepartment of Medical Oncology, Institut Gustave Roussy, F-94805 Villejuif, FranceInstitute of Toxicology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, GermanyInstitute for Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, D-45122 Essen, GermanyEA4553 Institut Claudius-Regaud, F-31052 Toulouse, FranceInstitut Curie, F-75248 Paris, FranceInstitut Curie, F-75248 Paris, FranceInstitut Curie, F-75248 Paris, FranceThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Medical Biosciences, Umeå University, SE-901 87 Umeå, SwedenDepartment of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, 807-8555 Kitakyushu, JapanCentre de Recherche des Cordeliers, F-75006 Paris, FrancePathology Departement, Université Paris Descartes V, F-75270 Paris, FranceThoracic Surgery Department, Hôtel Dieu, APHP, F-75004 Paris, FranceBevital AS, N-5021 Bergen, NorwaySection for Pharmacology, Institute of Medicine, University of Bergen, N-5021 Bergen, NorwayInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitute of Toxicology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, GermanyEA4553 Institut Claudius-Regaud, F-31052 Toulouse, FranceINSERM, U848, F-94805 Villejuif, FranceInstitute of Molecular Biosciences, University of Graz, A-8010 Graz, AustriaInstitut Curie, F-75248 Paris, FranceInstitute for Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, D-45122 Essen, GermanyThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USACentre de Recherche des Cordeliers, F-75006 Paris, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceInstitut Gustave Roussy, F-94805 Villejuif, FranceUniversité Paris-Sud XI, PArI Platform, F-91191 Gif-sur-Yvette, FranceINSERM, U848, F-94805 Villejuif, France Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC. http://www.sciencedirect.com/science/article/pii/S221112471200191X