Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
Department of Molecular Biotechnology and Health Sciences & Molecular Biotechnology Center, University of Torino, Torino, Italy.
Int J Biochem Cell Biol. 2022 Apr;145:106189. doi: 10.1016/j.biocel.2022.106189. Epub 2022 Feb 25.
Nicotinamide phosphoribosyltransferase (NAMPT) possesses a vital role in mammalian cells due to its activity as a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD) from nicotinamide. NAD is an essential redox cofactor, but it also functions as a substrate for NAD-consuming enzymes, regulating multiple cellular processes such as DNA repair and gene expression, fundamental to sustain tumor growth and survival and energetic needs. A common strategy that several tumor types adopt to sustain NAD synthesis is to over-express NAMPT. However, beside its intracellular functions, this enzyme has a second life outside of cells exerting cytokine-like functions and mediating pro-inflammatory conditions activating signaling pathways. While the effects of NAMPT/NAD axis on energetic metabolism in tumors has been well-established, increasing evidence demonstrated the impact of NAMPT over-expression (intra-/extra-cellular) on several tumor cellular processes, including DNA repair, gene expression, signaling pathways, proliferation, invasion, stemness, phenotype plasticity, metastatization, angiogenesis, immune regulation, and drug resistance. For all these reasons, NAMPT targeting has emerged as promising anti-cancer strategy to deplete NAD and impair cellular metabolism, but also to counteract the other NAMPT-related functions. In this review, we summarize the key role of NAMPT in multiple biological processes implicated in cancer biology and the impact of NAMPT inhibition as therapeutic strategy for cancer treatment.
烟酰胺磷酸核糖转移酶（NAMPT）作为烟酰胺腺嘌呤二核苷酸（NAD）生物合成中的限速酶，在哺乳动物细胞中具有重要作用，因为其活性。NAD 是一种必需的氧化还原辅因子，但它也作为 NAD 消耗酶的底物发挥作用，调节多种细胞过程，如 DNA 修复和基因表达，这对于维持肿瘤生长和存活以及能量需求至关重要。几种肿瘤类型采用的常见策略是过度表达 NAMPT 来维持 NAD 合成。然而，除了其细胞内功能外，这种酶在细胞外还有第二个生命，发挥细胞因子样功能，并介导促炎状态激活信号通路。虽然 NAMPT/NAD 轴对肿瘤能量代谢的影响已经得到很好的证实，但越来越多的证据表明 NAMPT 过度表达（细胞内/外）对几种肿瘤细胞过程的影响，包括 DNA 修复、基因表达、信号通路、增殖、侵袭、干性、表型可塑性、转移、血管生成、免疫调节和耐药性。基于所有这些原因，NAMPT 靶向已成为一种有前途的抗癌策略，可以消耗 NAD 和损害细胞代谢，但也可以对抗其他与 NAMPT 相关的功能。在这篇综述中，我们总结了 NAMPT 在癌症生物学中涉及的多种生物学过程中的关键作用，以及 NAMPT 抑制作为癌症治疗的治疗策略的影响。
