Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Genes and Development Year : 2018

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

Abstract

In BRAFV600E 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.

Domains

Cancer
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Dates and versions

inserm-02528273 , version 1 (01-04-2020)

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Mickaël Ohanna, Mickaël Cerezo, Nicolas Nottet, Karine Bille, Robin Didier, et al.. Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype. Genes and Development, 2018, 32 (5-6), pp.448-461. ⟨10.1101/gad.305854.117⟩. ⟨inserm-02528273⟩
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