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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Format: | Article |
Language: | English |
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Elsevier
2012-08-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471200191X |
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language |
English |
format |
Article |
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DOAJ |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S221112471200191X |
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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 |