Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype

被引：65

作者：

Ohanna, Mickael ^{[1
]}

Cerezo, Mickael ^{[1
,5
]}

Nottet, Nicolas ^{[2
]}

Bille, Karine ^{[1
]}

Didier, Robin ^{[1
]}

Beranger, Guillaume ^{[1
]}

Mograbi, Baharia ^{[3
]}

Rocchi, Stephane ^{[1
]}

Yvan-Charvet, Laurent ^{[4
]}

Ballotti, Robert ^{[1
]}

Bertolotto, Corine ^{[1
]}

机构：

[1] Univ Nice Cote dAzur, Equipe Labellisee Assoc Rech Canc ARC 2015, INSERM, Biol & Pathol Melanocytes,U1065,C3M, F-06204 Nice, France

[2] Univ Nice Cote dAzur, INSERM, C3M, F-06204 Nice, France

[3] Univ Nice Cote dAzur, INSERM, Equipe Labellisee ARC, U1081,IRCAN,UMR7284,CNRS, F-06107 Nice, France

[4] Univ Nice Cote dAzur, TeamATIP Avenir, INSERM, U1065,C3M, F-06204 Nice, France

[5] INSERM, U981, Villejuif, France

来源：

GENES & DEVELOPMENT | 2018年 / 32卷 / 5-6期

关键词：

melanoma; metabolism; NAD; targeted therapy; SIGNAL TRANSDUCER; PHASE-I; METABOLISM; MUTANT; TRANSCRIPTION; STAT5; MITF; IDENTIFICATION; PROLIFERATION; REGULATORS;

D O I：

10.1101/gad.305854.117

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：448 / 461

页数：14

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