Valentina Audrito, Vincenzo Gianluca Messana, Enrico Moiso, Nicoletta Vitale, Francesca Arruga, Lorenzo Brandimarte, Federica Gaudino, Elisa Pellegrino, Tiziana Vaisitti, Chiara Riganti, Roberto Piva, Silvia Deaglio
Serine-threonine protein kinase B-RAF ( BRAF) -mutated metastatic melanoma (MM) is a highly aggressive type of skin cancer. Treatment of MM patients using BRAF/MEK inhibitors (BRAFi/MEKi) eventually leads to drug resistance, limiting any clinical benefit. Herein, we demonstrated that the nicotinamide adenine dinucleotide (NAD)-biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) is a driving factor in BRAFi resistance development. Using stable and inducible NAMPT over-expression systems, we showed that forced NAMPT expression in MM BRAF -mutated cell lines led to increased energy production, MAPK activation, colony-formation capacity, and enhance tumorigenicity in vivo...
December 20, 2020: Cancers