Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

被引：107

作者：

Galluzzi, Lorenzo ^{[1
,2
]}

Vitale, Ilio ^{[1
,2
]}

Senovilla, Laura ^{[1
,2
]}

Olaussen, Ken Andre ^{[2
,3
]}

Pinna, Guillaume ^{[4
,5
]}

Eisenberg, Tobias ^{[6
]}

Goubar, Aicha ^{[2
,3
]}

Martins, Isabelle ^{[1
,2
]}

Michels, Judith ^{[1
,2
]}

Kratassiouk, Gueorgui ^{[4
,5
]}

Carmona-Gutierrez, Didac ^{[6
]}

Scoazec, Marie

Vacchelli, Erika ^{[1
,2
]}

Schlemmer, Frederic ^{[1
,2
]}

Kepp, Oliver ^{[1
,2
]}

Shen, Shensi ^{[1
,2
]}

Tailler, Maximilien ^{[1
,2
]}

Niso-Santano, Mireia ^{[1
,2
]}

Morselli, Eugenia ^{[1
,2
]}

Criollo, Alfredo ^{[1
,2
]}

Adjemian, Sandy ^{[1
,2
]}

Jemaa, Mohamed ^{[1
,2
]}

Chaba, Kariman ^{[7
,12
]}

Pailleret, Claire ^{[1
,2
]}

Michaud, Mickael ^{[1
,2
]}

Pietrocola, Federico ^{[1
,2
]}

Tajeddine, Nicolas ^{[1
,2
]}

Rouge, Thibault de La Motte ^{[13
]}

Araujo, Natalia ^{[4
,5
]}

Morozova, Nadya ^{[4
,5
]}

Robert, Thomas ^{[8
]}

Ripoche, Hugues ^{[14
]}

Commo, Frederic ^{[2
,3
]}

Besse, Benjamin ^{[9
]}

Validire, Pierre ^{[15
]}

Fouret, Pierre ^{[16
,17
,18
]}

Robin, Angelique ^{[2
,3
]}

Dorvault, Nicolas ^{[2
,3
]}

Girard, Philippe ^{[19
]}

Gouy, Sebastien ^{[10
]}

Pautier, Patricia ^{[9
]}

Jaegemann, Nora ^{[20
]}

Nickel, Ann-Christin ^{[21
]}

Marsili, Sabrina ^{[22
]}

Paccard, Caroline ^{[23
,24
,25
]}

Servant, Nicolas ^{[23
,24
,25
]}

Hupe, Philippe ^{[23
,24
,25
,26
]}

Behrens, Carmen ^{[27
]}

Behnam-Motlagh, Parviz ^{[28
]}

Kohno, Kimitoshi ^{[29
]}

机构：

[1] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France

[2] Univ Paris 11, F-94805 Villejuif, France

[3] Inst Gustave Roussy, INSERM, U981, F-94805 Villejuif, France

[4] Univ Paris 11, F-91191 Gif Sur Yvette, France

[5] CENS, Lab Leon Brillouin, CNRS, FRE3377, F-91191 Gif Sur Yvette, France

[6] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[7] Inst Gustave Roussy, Ctr Clin Invest Biotherapies Canc CICBT 507, F-94805 Villejuif, France

[8] Inst Gustave Roussy, Unite Genom Fonct & Bioinformat, F-94805 Villejuif, France

[9] Inst Gustave Roussy, Dept Med Oncol, F-94805 Villejuif, France

[10] Inst Gustave Roussy, Dept Surg, F-94805 Villejuif, France

[11] Inst Gustave Roussy, SITEP Phase Unit 1, F-94805 Villejuif, France

[12] Inst Gustave Roussy, INSERM, U1015, F-94805 Villejuif, France

[13] Grp Hosp Pitie Salpetriere, Med Oncol Serv, F-75651 Paris, France

[14] CNRS, UMR8200, F-94805 Villejuif, France

[15] Inst Mutualiste Montsouris, Serv Anat Pathol, F-75014 Paris, France

[16] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France

[17] Grp Hosp Pitie Salpetriere, Serv Anat Pathol, F-75651 Paris, France

[18] Univ Paris 06, F-75005 Paris, France

[19] Inst Mutualiste Montsouris, Dept Thorac, F-75014 Paris, France

[20] Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Toxicol, D-85764 Neuherberg, Germany

[21] Univ Duisburg Essen, Sch Med, Inst Cell Biol Canc Res, D-45122 Essen, Germany

[22] Inst Claudius Regaud, EA4553, F-31052 Toulouse, France

[23] Inst Curie, F-75248 Paris, France

[24] INSERM, U900, F-75248 Paris, France

[25] Mines ParisTech, F-77300 Fontainebleau, France

[26] CNRS, UMR144, F-75248 Paris, France

[27] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[28] Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden

[29] Univ Occupat & Environm Hlth, Sch Med, Dept Mol Biol, Kitakyushu, Fukuoka 8078555, Japan

[30] Ctr Rech Cordeliers, F-75006 Paris, France

[31] Univ Paris 05, Dept Pathol, F-75270 Paris, France

[32] Hop Hotel Dieu, APHP, Dept Thorac Surg, F-75004 Paris, France

[33] Bevital AS, N-5021 Bergen, Norway

[34] Univ Bergen, Inst Med, Pharmacol Sect, N-5021 Bergen, Norway

[35] INSERM, U872, F-75006 Paris, France

[36] Hop Europeen Georges Pompidou, AP HP, F-75908 Paris, France

来源：

CELL REPORTS | 2012年 / 2卷 / 02期

关键词：

MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; GROWTH-FACTOR; KINASE; INHIBITION; APOPTOSIS; CELLS; ALK; P53; INFLAMMATION; DEATH;

D O I：

10.1016/j.celrep.2012.06.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：257 / 269

页数：13

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