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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.S.* ; Tailler, M.* ; Niso-Santano, M.* ; Morselli, E.* ; Criollo, A.* ; Adjemian, S.* ; Jemaa, M.* ; Chaba, K.* ; Pailleret, C.* ; Michaud, M.* ; Pietrocola, F.* ; Tajeddine, N.* ; Rouge, T.D.* ; 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, A.C.* ; Marsili, S.* ; Paccard, C.* ; Servant, N.* ; Hupé, P.* ; Behrens, C.* ; Behnam-Motlagh, P.* ; Kohno, K.* ; Cremer, I.* ; Damotte, D.* ; Alifano, M.* ; Midttun, O.* ; Ueland, P.M.* ; Lazar, V.* ; Dessen, P.* ; Zischka, H. ; Chatelut, E.* ; Castedo, M.* ; Madeo, F.* ; Barillot, E.* ; Thomale, J.* ; Wistuba, I.I.* ; Sautes-Fridman, C.* ; Zitvogel, L.* ; Soria, J.C.* ; Harel-Bellan, A.* ; Kroemer, G.*

Prognostic impact of vitamin B6 metabolism in lung cancer.

Cell Rep. 2, 257-269 (2012)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CELL-DEATH; GROWTH-FACTOR; APOPTOSIS; KINASE; INHIBITION; ALK; P53; INFLAMMATION; HALLMARKS
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 2, Issue: 2, Pages: 257-269 Article Number: , Supplement: ,
Publisher Cell Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)