Nicotinamide phosphoribosyltransferase: Biology, role in cancer, and novel drug target

Abstract

The nicotinamide adenine dinucleotide (NAD+) pool is an important electron exchanger in tumor biology. The salvage pathway plays an important role in the regulation of the levels of cellular NAD+ biosynthesis and the nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme of this pathway. Thus, NAMPT plays a key role in the levels of the NAD+ pool. NAMPT levels in several types of cancer, both solid and hematological cancers, are found to be high compared to the normal tissue. In these tumors, NAMPT overexpression induces an increase in tumorigenic properties. Increased transcription levels of NAMPT result in an increased rate of growth, resistance to cell death, and epidermal-to-mesenchymal transition imparting cancer stem cell-like properties in tumorigenic cells. Main stemness signaling pathways such as Notch, Hippo, Sonic, and Wnt are associated with increased NAMPT transcription levels. NAMPT-induced oncogenic phenotype is also associated with worse prognosis and resistance to therapy in human tumors. Therefore, NAMPT could be an interesting enzyme to consider as probable therapeutic target.