Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Galluzzi, Lorenzo; Vitale, Ilio; Senovilla, Laura; Olaussen, Ken A.; Pinna, Guillaume; Eisenberg, Tobias; Goubar, Aïcha; Martins, Isabelle; Michels, Judith; Kratassiouk, Gueorgui; Carmona-Gutiérrez, Didac; Scoazec, Marie; Schlemmer, F.; Kepp, Oliver; Shen, Shensi; Tailler, Maximilien; Niso-Santano, Mireia; Morselli, Eugenia; Criollo, Alfredo; Adjemian, Sandy; Jèmaà, Mohamed; Chaba, Kariman; Pailleret, Claire; Michaud, Mickaël; Pietrocola, Federico; Tajeddine, Nicolas; Rouge, Thibault De La Motte; Araújo, Natalia M.; Morozova, Nadya; Thomas, Robert; Ripoche, Hugues; Commo, Frédéric; Besse, Benjamin; Validire, Pierre; Fouret, Pierre; Robin, Angélique; Dorvault, Nicolas; Girard, Philippe; Gouy, Sébastien; Pautier, Patricia; Jägemann, Nora; Nickel, Ann-Christin; Marsili, Sabrina; Paccard, Caroline; Servant, Nicolas; Hupé, Philippe; Behrens, Carmen; Behnam‐Motlagh, Parviz; Kohno, Kimitoshi; Cremer, Isabelle; Damotte, Diane; Alifano, Marco; Midttun, Øivind; Ueland, Per Magne; Lazar, Vladimir; Dessen, Philippe; Zischka, Hans; Chatelut, Étienne; Castedo, Maria; Madeo, Frank; Barillot, Emmanuel; Thomale, Jürgen; Wistuba, Ignacio I.; Sautès-Fridman, Catheriné; Zitvogel, Laurence; Soria, Jean‐Charles; Harel‐Bellan, Annick; Kroemer, Guido

doi:10.1016/j.celrep.2012.11.007

Cited by 20 publications

(49 citation statements)

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“…siRNAs were transfected by means of the HiPerfect transfection reagent (Qiagen, Hilden, Germany), as previously described. 55,56 siRNA array screening. Bio-one mClear 384-well plates (Greiner Bio One, Kremsmuenster, Austria) were printed with 3.125 ng individual siRNAs (Qiagen) designed to target 250 different human proteins implicated in cell death and stress-response pathways.…”

Section: Methodsmentioning

confidence: 99%

“…For immunoblotting, approximately 1 Â 10 6 cells were washed with cold PBS and lysed as previously described. 55,56 Fifty micrograms of proteins were then separated according to molecular weight on NuPAGE Novex Bis-Tris 4-12% pre-cast gels (Life Technologies) and electrotransferred to nitrocellulose membranes (Bio-Rad, Hercules, CA, USA). Unspecific binding sites were blocked by incubating membranes for 1 h in 0.05% Tween 20 (v/v in TBS) supplemented with 5% non-fat powdered milk, followed by overnight incubation at 4 1C with primary antibodies specific for BECN1 (Santa-Cruz Biotechnology, Santa Cruz, CA, USA) or CASP8 (Calbiochem-Merck Millipore, Billerica, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

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Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Sukkurwala¹,

Martins²,

Wang³

et al. 2013

Cell Death Differ

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The exposure of calreticulin (CRT) on the surface of stressed and dying cancer cells facilitates their uptake by dendritic cells and the subsequent presentation of tumor-associated antigens to T lymphocytes, hence stimulating an anticancer immune response. The chemotherapeutic agent mitoxantrone (MTX) can stimulate the peripheral relocation of CRT in both human and yeast cells, suggesting that the CRT exposure pathway is phylogenetically conserved. Here, we show that pheromones can act as physiological inducers of CRT exposure in yeast cells, thereby facilitating the formation of mating conjugates, and that a largespectrum inhibitor of G protein-coupled receptors (which resemble the yeast pheromone receptor) prevents CRT exposure in human cancer cells exposed to MTX. An RNA interference screen as well as transcriptome analyses revealed that chemokines, in particular human CXCL8 (best known as interleukin-8) and its mouse ortholog Cxcl2, are involved in the immunogenic translocation of CRT to the outer leaflet of the plasma membrane. MTX stimulated the production of CXCL8 by human cancer cells in vitro and that of Cxcl2 by murine tumors in vivo. The knockdown of CXCL8/Cxcl2 receptors (CXCR1/Cxcr1 and Cxcr2) reduced MTX-induced CRT exposure in both human and murine cancer cells, as well as the capacity of the latter-on exposure to MTX-to elicit an anticancer immune response in vivo. Conversely, the addition of exogenous Cxcl2 increased the immunogenicity of dying cells in a CRT-dependent manner. Altogether, these results identify autocrine and paracrine chemokine signaling circuitries that modulate CRT exposure and the immunogenicity of cell death.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Sukkurwala¹,

Martins²,

Wang³

et al. 2013

Cell Death Differ

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“…1,3,4 Importantly, some -but not all -cell death inducers are capable of eliciting ICD, 35 and this property cannot be anticipated by structural or functional considerations. 3,[36][37][38] Indeed, while cisplatin and oxaliplatin both exert cytostatic/cytotoxic effects as they induce inter-and intra-strand DNA adducts, [39][40][41][42] only the latter triggers bona fide ICD as it provokes a pre-mortem ER stress response. 43,44 Thus, although assays for the detection of surrogate ICD markers are available, 45 the gold standard approach for determining whether a cytotoxic intervention provokes bona fide ICD still relies on vaccination experiments involving murine cancer cells and syngeneic, immunocompetent mice.…”

Section: Introductionmentioning

confidence: 99%

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

et al. 2015

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“…In line with a key role for vitamin B6 metabolism in the demise of malignant cells exposed to adverse micro-environmental conditions, we also found that high expression levels of PDXK (as measured by immunohistochemistry in tumor biopsies) positively influence disease outcome in non-small cell lung cancer (NSCLC) patients, irrespective of whether they are treated or not. 6 The molecular mechanisms whereby PN sensitizes cancer cells to the cytotoxic potential of various chemical, physical and metabolic insults remain to be precisely determined, but may relate to an accrued oxidative response. 6 In the specific case of CDDP, the chemosensitizing effects of PN also reflect an increased intracellular accumulation of the drug that depends on PDXK1 but not on known CDDP transporters such as solute carrier family 31, member 1 (SLC31A1, best known as CTR1) and ATPase, Cu 2C transporting, b polypeptide (ATP7B).…”

mentioning

confidence: 99%

“…6,7 Thus, the administration of pyridoxine (PN), a cell-permeant precursor of the active form of vitamin B6 (i.e., pyridoxal-5-phosphate), sensitizes cancer cells of various histological origin to the cytotoxic effects of multiple chemotherapeutics (including CDDP), irradiation, hyperthermia, nutrient deprivation, and hypoxia, just to mention a few examples. Notably, such an effect strictly depends on the presence of pyridoxal kinase (PDXK), the enzyme that phosphorylates vitamin B6 precursors to synthesize pyridoxal-5-phosphate.…”

mentioning

confidence: 99%