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  • 11
    Publication Date: 2018-03-29
    Description: In BRAF V600E melanoma cells, a global metabolomic analysis discloses a decrease in nicotinamide adenine dinucleotide (NAD + ) levels upon PLX4032 treatment that is conveyed by a STAT5 inhibition and a transcriptional regulation of the nicotinamide phosphoribosyltransferase (NAMPT) gene. NAMPT inhibition decreases melanoma cell proliferation both in vitro and in vivo, while forced NAMPT expression renders melanoma cells resistant to PLX4032. NAMPT expression induces transcriptomic and epigenetic reshufflings that steer melanoma cells toward an invasive phenotype associated with resistance to targeted therapies and immunotherapies. Therefore, NAMPT, the key enzyme in the NAD + salvage pathway, appears as a rational target in targeted therapy-resistant melanoma cells and a key player in phenotypic plasticity of melanoma cells.
    Print ISSN: 0890-9369
    Topics: Biology
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  • 12
    Publication Date: 2011-10-21
    Description: So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (PsiKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bertolotto, Corine -- Lesueur, Fabienne -- Giuliano, Sandy -- Strub, Thomas -- de Lichy, Mahaut -- Bille, Karine -- Dessen, Philippe -- d'Hayer, Benoit -- Mohamdi, Hamida -- Remenieras, Audrey -- Maubec, Eve -- de la Fouchardiere, Arnaud -- Molinie, Vincent -- Vabres, Pierre -- Dalle, Stephane -- Poulalhon, Nicolas -- Martin-Denavit, Tanguy -- Thomas, Luc -- Andry-Benzaquen, Pascale -- Dupin, Nicolas -- Boitier, Francoise -- Rossi, Annick -- Perrot, Jean-Luc -- Labeille, Bruno -- Robert, Caroline -- Escudier, Bernard -- Caron, Olivier -- Brugieres, Laurence -- Saule, Simon -- Gardie, Betty -- Gad, Sophie -- Richard, Stephane -- Couturier, Jerome -- Teh, Bin Tean -- Ghiorzo, Paola -- Pastorino, Lorenza -- Puig, Susana -- Badenas, Celia -- Olsson, Hakan -- Ingvar, Christian -- Rouleau, Etienne -- Lidereau, Rosette -- Bahadoran, Philippe -- Vielh, Philippe -- Corda, Eve -- Blanche, Helene -- Zelenika, Diana -- Galan, Pilar -- French Familial Melanoma Study Group -- Aubin, Francois -- Bachollet, Bertrand -- Becuwe, Celine -- Berthet, Pascaline -- Bignon, Yves Jean -- Bonadona, Valerie -- Bonafe, Jean-Louis -- Bonnet-Dupeyron, Marie-Noelle -- Cambazard, Frederic -- Chevrant-Breton, Jacqueline -- Coupier, Isabelle -- Dalac, Sophie -- Demange, Liliane -- d'Incan, Michel -- Dugast, Catherine -- Faivre, Laurence -- Vincent-Fetita, Lynda -- Gauthier-Villars, Marion -- Gilbert, Brigitte -- Grange, Florent -- Grob, Jean-Jacques -- Humbert, Philippe -- Janin, Nicolas -- Joly, Pascal -- Kerob, Delphine -- Lasset, Christine -- Leroux, Dominique -- Levang, Julien -- Limacher, Jean-Marc -- Livideanu, Cristina -- Longy, Michel -- Lortholary, Alain -- Stoppa-Lyonnet, Dominique -- Mansard, Sandrine -- Mansuy, Ludovic -- Marrou, Karine -- Mateus, Christine -- Maugard, Christine -- Meyer, Nicolas -- Nogues, Catherine -- Souteyrand, Pierre -- Venat-Bouvet, Laurence -- Zattara, Helene -- Chaudru, Valerie -- Lenoir, Gilbert M -- Lathrop, Mark -- Davidson, Irwin -- Avril, Marie-Francoise -- Demenais, Florence -- Ballotti, Robert -- Bressac-de Paillerets, Brigitte -- England -- Nature. 2011 Oct 19;480(7375):94-8. doi: 10.1038/nature10539.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] INSERM, U895 (equipe 1), Equipe labelisee Ligue Contre le Cancer, C3M, 06204 Nice, France [2] Universite of Nice Sophia-Antipolis, UFR Medecine, 06204 Nice, France [3] Centre Hospitalier Universitaire de Nice, Service de Dermatologie, 06204 Nice, France [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22012259" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma, Renal Cell/*genetics ; Cell Movement/genetics ; Gene Frequency ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Melanoma/*genetics ; Microphthalmia-Associated Transcription Factor/*genetics ; Neoplasm Invasiveness/genetics ; Sumoylation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 13
    Publication Date: 2015-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bertolotto, Corine -- Lesueur, Fabienne -- Giuliano, Sandy -- Strub, Thomas -- de Lichy, Mahaut -- Bille, Karine -- Dessen, Philippe -- d'Hayer, Benoit -- Mohamdi, Hamida -- Remenieras, Audrey -- Maubec, Eve -- de la Fouchardiere, Arnaud -- Molinie, Vincent -- Vabres, Pierre -- Dalle, Stephane -- Poulalhon, Nicolas -- Martin-Denavit, Tanguy -- Thomas, Luc -- Andry-Benzaquen, Pascale -- Dupin, Nicolas -- Boitier, Francoise -- Rossi, Annick -- Perrot, Jean-Luc -- Labeille, Bruno -- Robert, Caroline -- Escudier, Bernard -- Caron, Olivier -- Brugieres, Laurence -- Saule, Simon -- Gardie, Betty -- Gad, Sophie -- Richard, Stephane -- Couturier, Jerome -- Teh, Bin Tean -- Ghiorzo, Paola -- Pastorino, Lorenza -- Puig, Susana -- Badenas, Celia -- Olsson, Hakan -- Ingvar, Christian -- Rouleau, Etienne -- Lidereau, Rosette -- Bahadoran, Philippe -- Vielh, Philippe -- Corda, Eve -- Blanche, Helene -- Zelenika, Diana -- Galan, Pilar -- French Familial Melanoma Study Group -- Chaudru, Valerie -- Lenoir, Gilbert M -- Lathrop, Mark -- Davidson, Irwin -- Avril, Marie-Francoise -- Demenais, Florence -- Ballotti, Robert -- Bressac-de Paillerets, Brigitte -- England -- Nature. 2016 Mar 3;531(7592):126. doi: 10.1038/nature16158. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633630" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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