title: Prognostic impact of vitamin B6 metabolism in lung cancer.
abstract: 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.
authors.affiliation: INSERM, U, Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.forename: Ken André
authors.initials: KA
authors.lastname: Olaussen
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pinna
authors.forename: Tobias
authors.initials: T
authors.lastname: Eisenberg
authors.forename: Aïcha
authors.initials: A
authors.lastname: Goubar
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Judith
authors.initials: J
authors.lastname: Michels
authors.forename: Gueorgui
authors.initials: G
authors.lastname: Kratassiouk
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.forename: Marie
authors.initials: M
authors.lastname: Scoazec
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.forename: Frederic
authors.initials: F
authors.lastname: Schlemmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Shensi
authors.initials: S
authors.lastname: Shen
authors.forename: Maximilien
authors.initials: M
authors.lastname: Tailler
authors.forename: Mireia
authors.initials: M
authors.lastname: Niso-Santano
authors.forename: Eugenia
authors.initials: E
authors.lastname: Morselli
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jemaà
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.forename: Claire
authors.initials: C
authors.lastname: Pailleret
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tajeddine
authors.forename: Thibault
authors.initials: T
authors.lastname: de La Motte Rouge
authors.forename: Natalia
authors.initials: N
authors.lastname: Araujo
authors.forename: Nadya
authors.initials: N
authors.lastname: Morozova
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Hugues
authors.initials: H
authors.lastname: Ripoche
authors.forename: Frederic
authors.initials: F
authors.lastname: Commo
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouret
authors.forename: Angélique
authors.initials: A
authors.lastname: Robin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dorvault
authors.forename: Philippe
authors.initials: P
authors.lastname: Girard
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gouy
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Nora
authors.initials: N
authors.lastname: Jägemann
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Nickel
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marsili
authors.forename: Caroline
authors.initials: C
authors.lastname: Paccard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Parviz
authors.initials: P
authors.lastname: Behnam-Motlagh
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.forename: Oivind
authors.initials: O
authors.lastname: Midttun
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Hans
authors.initials: H
authors.lastname: Zischka
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Juergen
authors.initials: J
authors.lastname: Thomale
authors.forename: Ignacio Ivan
authors.initials: II
authors.lastname: Wistuba
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011731:Pyridoxal Kinase / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate; D025101:Vitamin B 6 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D025101:Vitamin B 6; D011731:Pyridoxal Kinase; D002945:Cisplatin