2019
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Leclerc, J; Garandeau, D; Pandiani, C; Gaudel, C; Bille, K; Nottet, N; Garcia, V; Colosetti, P; Pagnotta, S; Bahadoran, P; Tondeur, G; Mograbi, B; Dalle, S; Caramel, J; Levade, T; Ballotti, R; Andrieu-Abadie, N; Bertolotto, C Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells. Article de journal Oncogene, 38 (8), p. 1282-1295, 2019. Résumé | Liens | BibTeX @article{Leclerc2019,
title = {Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells.},
author = {Leclerc, J. and Garandeau, D. and Pandiani, C. and Gaudel, C. and Bille, K. and Nottet, N. and Garcia, V. and Colosetti, P. and Pagnotta, S. and Bahadoran, P. and Tondeur, G. and Mograbi, B. and Dalle, S. and Caramel, J. and Levade, T. and Ballotti, R. and Andrieu-Abadie, N. and Bertolotto, C. },
url = {https://www.nature.com/articles/s41388-018-0500-0},
doi = {doi: 10.1038/s41388-018-0500-0},
year = {2019},
date = {2019-02-21},
journal = {Oncogene},
volume = {38},
number = {8},
pages = {1282-1295},
abstract = {Phenotypic plasticity and subsequent generation of intratumoral heterogeneity underly key traits in malignant melanoma such as drug resistance and metastasis. Melanoma plasticity promotes a switch between proliferative and invasive phenotypes characterized by different transcriptional programs of which MITF is a critical regulator. Here, we show that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK signaling cascade. In line with that, human melanoma biopsies revealed heterogeneous staining of ASAH1 and low ASAH1 expression at the melanoma invasive front. We also identified ASAH1 as a new target of MITF, thereby involving MITF in the regulation of sphingolipid metabolism. Together, our findings provide new cues to the mechanisms underlying the phenotypic plasticity of melanoma cells and identify new anti-metastatic targets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Phenotypic plasticity and subsequent generation of intratumoral heterogeneity underly key traits in malignant melanoma such as drug resistance and metastasis. Melanoma plasticity promotes a switch between proliferative and invasive phenotypes characterized by different transcriptional programs of which MITF is a critical regulator. Here, we show that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK signaling cascade. In line with that, human melanoma biopsies revealed heterogeneous staining of ASAH1 and low ASAH1 expression at the melanoma invasive front. We also identified ASAH1 as a new target of MITF, thereby involving MITF in the regulation of sphingolipid metabolism. Together, our findings provide new cues to the mechanisms underlying the phenotypic plasticity of melanoma cells and identify new anti-metastatic targets. |
Garandeau, D; Noujarède, J; Leclerc, J; Imbert, C; Garcia, V; Bats, ML. ; Rambow, F; Gilhodes, J; Filleron, T; Meyer, N; Brayer, S; Arcucci, S; Tartare-Deckert, S; Ségui, B; Marine, JC. ; Levade, T; Bertolotto, C; Andrieu-Abadie, N Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas. Article de journal Mol Cancer Ther, 18 (2), p. 289-300, 2019. Résumé | Liens | BibTeX @article{Garandeau2019,
title = {Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas.},
author = {Garandeau, D. and Noujarède, J. and Leclerc, J. and Imbert, C. and Garcia, V. and Bats, ML. and Rambow, F. and Gilhodes, J. and Filleron, T. and Meyer, N. and Brayer, S. and Arcucci, S. and Tartare-Deckert, S. and Ségui, B. and Marine, JC. and Levade, T. and Bertolotto, C. and Andrieu-Abadie, N.},
url = {https://mct.aacrjournals.org/content/18/2/289.long},
doi = {doi: 10.1158/1535-7163.MCT-17-1141},
year = {2019},
date = {2019-02-01},
journal = {Mol Cancer Ther},
volume = {18},
number = {2},
pages = {289-300},
abstract = {BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAFV600E-mutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFi-resistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAFV600E-mutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFi-resistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy. |
2017
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Bertrand, F; Montfort, A; Marcheteau, E; Imbert, C; Gilhodes, J; Filleron, T; Rochaix, P; Andrieu-Abadie, N; Levade, T; Meyer, N; Colacios, C; Ségui, B TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma. Article de journal Nat Commun, 8 (1), p. 2256, 2017. Résumé | Liens | BibTeX @article{F2017,
title = {TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma.},
author = {Bertrand, F. and Montfort, A. and Marcheteau, E. and Imbert, C. and Gilhodes, J. and Filleron, T. and Rochaix, P. and Andrieu-Abadie, N. and Levade, T. and Meyer, N. and Colacios, C. and Ségui, B.},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741628/},
doi = {doi: 10.1038/s41467-017-02358-7},
year = {2017},
date = {2017-12-22},
journal = {Nat Commun},
volume = {8},
number = {1},
pages = {2256},
abstract = {Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma. Herein, our results indicate that TNF or TNFR1 blockade synergizes with anti-PD-1 on anti-cancer immune responses towards solid cancers. Mechanistically, TNF blockade prevents anti-PD-1-induced TIL cell death as well as PD-L1 and TIM-3 expression. TNF expression positively correlates with expression of PD-L1 and TIM-3 in human melanoma specimens. This study provides a strong rationale to develop a combination therapy based on the use of anti-PD-1 and anti-TNF in cancer patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma. Herein, our results indicate that TNF or TNFR1 blockade synergizes with anti-PD-1 on anti-cancer immune responses towards solid cancers. Mechanistically, TNF blockade prevents anti-PD-1-induced TIL cell death as well as PD-L1 and TIM-3 expression. TNF expression positively correlates with expression of PD-L1 and TIM-3 in human melanoma specimens. This study provides a strong rationale to develop a combination therapy based on the use of anti-PD-1 and anti-TNF in cancer patients. |
2016
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Mrad, M; Imbert, C; Garcia, V; Rambow, F; Therville, N; Carpentier, S; Segui, B; Levade, T; Azar, R; Marine, J C; Diab-Assaf, M; Colacios, C; Andrieu-Abadie, N Downregulation of sphingosine kinase-1 induces protective tumor immunity by promoting M1 macrophage response in melanoma Article de journal Oncotarget, 7 (44), p. 71873-71886, 2016, ISSN: 1949-2553 (Electronic)
1949-2553 (Linking). Liens | BibTeX @article{RN1b,
title = {Downregulation of sphingosine kinase-1 induces protective tumor immunity by promoting M1 macrophage response in melanoma},
author = {Mrad, M. and Imbert, C. and Garcia, V. and Rambow, F. and Therville, N. and Carpentier, S. and Segui, B. and Levade, T. and Azar, R. and Marine, J. C. and Diab-Assaf, M. and Colacios, C. and Andrieu-Abadie, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27708249},
doi = {10.18632/oncotarget.12380},
issn = {1949-2553 (Electronic)
1949-2553 (Linking)},
year = {2016},
date = {2016-01-01},
journal = {Oncotarget},
volume = {7},
number = {44},
pages = {71873-71886},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2015
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Bertrand, F; Rochotte, J; Colacios, C; Montfort, A; Tilkin-Mariame, A F; Touriol, C; Rochaix, P; Lajoie-Mazenc, I; Andrieu-Abadie, N; Levade, T; Benoist, H; Segui, B Blocking Tumor Necrosis Factor alpha Enhances CD8 T-cell-Dependent Immunity in Experimental Melanoma Article de journal Cancer Res, 75 (13), p. 2619-28, 2015, ISSN: 1538-7445 (Electronic)
0008-5472 (Linking). Liens | BibTeX @article{RN2b,
title = {Blocking Tumor Necrosis Factor alpha Enhances CD8 T-cell-Dependent Immunity in Experimental Melanoma},
author = {Bertrand, F. and Rochotte, J. and Colacios, C. and Montfort, A. and Tilkin-Mariame, A. F. and Touriol, C. and Rochaix, P. and Lajoie-Mazenc, I. and Andrieu-Abadie, N. and Levade, T. and Benoist, H. and Segui, B.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25977337},
doi = {10.1158/0008-5472.CAN-14-2524},
issn = {1538-7445 (Electronic)
0008-5472 (Linking)},
year = {2015},
date = {2015-01-01},
journal = {Cancer Res},
volume = {75},
number = {13},
pages = {2619-28},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2014
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Albinet, V; Bats, M L; Huwiler, A; Rochaix, P; Chevreau, C; Segui, B; Levade, T; Andrieu-Abadie, N Dual role of sphingosine kinase-1 in promoting the differentiation of dermal fibroblasts and the dissemination of melanoma cells Article de journal Oncogene, 33 (26), p. 3364-73, 2014, ISSN: 1476-5594 (Electronic)
0950-9232 (Linking). Liens | BibTeX @article{RN3b,
title = {Dual role of sphingosine kinase-1 in promoting the differentiation of dermal fibroblasts and the dissemination of melanoma cells},
author = {Albinet, V. and Bats, M. L. and Huwiler, A. and Rochaix, P. and Chevreau, C. and Segui, B. and Levade, T. and Andrieu-Abadie, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23893239},
doi = {10.1038/onc.2013.303},
issn = {1476-5594 (Electronic)
0950-9232 (Linking)},
year = {2014},
date = {2014-01-01},
journal = {Oncogene},
volume = {33},
number = {26},
pages = {3364-73},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2013
|
Sorli, S C; Colie, S; Albinet, V; Dubrac, A; Touriol, C; Guilbaud, N; Bedia, C; Fabrias, G; Casas, J; Segui, B; Levade, T; Andrieu-Abadie, N The nonlysosomal beta-glucosidase GBA2 promotes endoplasmic reticulum stress and impairs tumorigenicity of human melanoma cells Article de journal FASEB J, 27 (2), p. 489-98, 2013, ISSN: 1530-6860 (Electronic)
0892-6638 (Linking). Liens | BibTeX @article{RN4b,
title = {The nonlysosomal beta-glucosidase GBA2 promotes endoplasmic reticulum stress and impairs tumorigenicity of human melanoma cells},
author = {Sorli, S. C. and Colie, S. and Albinet, V. and Dubrac, A. and Touriol, C. and Guilbaud, N. and Bedia, C. and Fabrias, G. and Casas, J. and Segui, B. and Levade, T. and Andrieu-Abadie, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23073830},
doi = {10.1096/fj.12-215152},
issn = {1530-6860 (Electronic)
0892-6638 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {FASEB J},
volume = {27},
number = {2},
pages = {489-98},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2012
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Lafont, E; Dupont, R; Andrieu-Abadie, N; Okazaki, T; Schulze-Osthoff, K; Levade, T; Benoist, H; Segui, B Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis Article de journal Biochim Biophys Acta, 1821 (4), p. 684-93, 2012, ISSN: 0006-3002 (Print)
0006-3002 (Linking). Liens | BibTeX @article{RN5b,
title = {Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis},
author = {Lafont, E. and Dupont, R. and Andrieu-Abadie, N. and Okazaki, T. and Schulze-Osthoff, K. and Levade, T. and Benoist, H. and Segui, B.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22306364},
doi = {10.1016/j.bbalip.2012.01.012},
issn = {0006-3002 (Print)
0006-3002 (Linking)},
year = {2012},
date = {2012-01-01},
journal = {Biochim Biophys Acta},
volume = {1821},
number = {4},
pages = {684-93},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2011
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Bedia, C; Casas, J; Andrieu-Abadie, N; Fabrias, G; Levade, T Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine Article de journal J Biol Chem, 286 (32), p. 28200-9, 2011, ISSN: 1083-351X (Electronic)
0021-9258 (Linking). Liens | BibTeX @article{RN6b,
title = {Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine},
author = {Bedia, C. and Casas, J. and Andrieu-Abadie, N. and Fabrias, G. and Levade, T.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/21700700},
doi = {10.1074/jbc.M110.216382},
issn = {1083-351X (Electronic)
0021-9258 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {J Biol Chem},
volume = {286},
number = {32},
pages = {28200-9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Sabourdy, F; Selves, J; Astudillo, L; Laurent, C; Brousset, P; Delisle, M B; Therville, N; Andrieu-Abadie, N; Segui, B; Recher, C; Levade, T Is active acid sphingomyelinase required for the antiproliferative response to rituximab? Article de journal Blood, 117 (13), p. 3695-6, 2011, ISSN: 1528-0020 (Electronic)
0006-4971 (Linking). Liens | BibTeX @article{RN7b,
title = {Is active acid sphingomyelinase required for the antiproliferative response to rituximab?},
author = {Sabourdy, F. and Selves, J. and Astudillo, L. and Laurent, C. and Brousset, P. and Delisle, M. B. and Therville, N. and Andrieu-Abadie, N. and Segui, B. and Recher, C. and Levade, T.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/21454466},
doi = {10.1182/blood-2010-11-318493},
issn = {1528-0020 (Electronic)
0006-4971 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {Blood},
volume = {117},
number = {13},
pages = {3695-6},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2010
|
Lafont, E; Milhas, D; Carpentier, S; Garcia, V; Jin, Z X; Umehara, H; Okazaki, T; Schulze-Osthoff, K; Levade, T; Benoist, H; Segui, B Caspase-mediated inhibition of sphingomyelin synthesis is involved in FasL-triggered cell death Article de journal Cell Death Differ, 17 (4), p. 642-54, 2010, ISSN: 1476-5403 (Electronic)
1350-9047 (Linking). Liens | BibTeX @article{RN9b,
title = {Caspase-mediated inhibition of sphingomyelin synthesis is involved in FasL-triggered cell death},
author = {Lafont, E. and Milhas, D. and Carpentier, S. and Garcia, V. and Jin, Z. X. and Umehara, H. and Okazaki, T. and Schulze-Osthoff, K. and Levade, T. and Benoist, H. and Segui, B.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19779494},
doi = {10.1038/cdd.2009.130},
issn = {1476-5403 (Electronic)
1350-9047 (Linking)},
year = {2010},
date = {2010-01-01},
journal = {Cell Death Differ},
volume = {17},
number = {4},
pages = {642-54},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2009
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Colie, S; Van Veldhoven, P P; Kedjouar, B; Bedia, C; Albinet, V; Sorli, S C; Garcia, V; Djavaheri-Mergny, M; Bauvy, C; Codogno, P; Levade, T; Andrieu-Abadie, N Disruption of sphingosine 1-phosphate lyase confers resistance to chemotherapy and promotes oncogenesis through Bcl-2/Bcl-xL upregulation Article de journal Cancer Res, 69 (24), p. 9346-53, 2009, ISSN: 1538-7445 (Electronic)
0008-5472 (Linking). Liens | BibTeX @article{RN8b,
title = {Disruption of sphingosine 1-phosphate lyase confers resistance to chemotherapy and promotes oncogenesis through Bcl-2/Bcl-xL upregulation},
author = {Colie, S. and Van Veldhoven, P. P. and Kedjouar, B. and Bedia, C. and Albinet, V. and Sorli, S. C. and Garcia, V. and Djavaheri-Mergny, M. and Bauvy, C. and Codogno, P. and Levade, T. and Andrieu-Abadie, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19934311},
doi = {10.1158/0008-5472.CAN-09-2198},
issn = {1538-7445 (Electronic)
0008-5472 (Linking)},
year = {2009},
date = {2009-01-01},
journal = {Cancer Res},
volume = {69},
number = {24},
pages = {9346-53},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Salma, Y; Lafont, E; Therville, N; Carpentier, S; Bonnafe, M J; Levade, T; Genisson, Y; Andrieu-Abadie, N The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism Article de journal Biochem Pharmacol, 78 (5), p. 477-85, 2009, ISSN: 1873-2968 (Electronic)
0006-2952 (Linking). Liens | BibTeX @article{RN10b,
title = {The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism},
author = {Salma, Y. and Lafont, E. and Therville, N. and Carpentier, S. and Bonnafe, M. J. and Levade, T. and Genisson, Y. and Andrieu-Abadie, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19433071},
doi = {10.1016/j.bcp.2009.05.002},
issn = {1873-2968 (Electronic)
0006-2952 (Linking)},
year = {2009},
date = {2009-01-01},
journal = {Biochem Pharmacol},
volume = {78},
number = {5},
pages = {477-85},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
