Chen Hang, Wang Shiyu, Zhang Haiyuan, Nice Edouard C, Huang Canhua
a Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education & Department of Neurology , The Affiliated Hospital of Hainan Medical College , Haikou , China.
b Department of Biochemistry and Molecular Biology , Monash University , Clayton , Australia.
Expert Rev Anticancer Ther. 2016 Aug;16(8):827-38. doi: 10.1080/14737140.2016.1190649. Epub 2016 Jul 5.
Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes the first step in the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway. Aberrant NAD metabolism was associated with oncogenic signal transduction, suggesting the critical roles of Nampt in tumorigenesis and metastasis. Additionally, Nampt can be secreted out of the cell, and this extracellular form of Nampt (eNampt) was shown to induce inflammation and angiogenesis due to its cytokine activity, which may also be involved in carcinogenesis.
This article reviews recent advances in the studies of Nampt in carcinogenesis, with a special highlight on Nampt inhibitors and future clinical application, including cancer diagnosis, prognosis and therapy. Expert commentary: Nampt not only maintains the balance of cellular metabolism, but also has a profound influence on multiple aspects of carcinogenesis. Therefore, elucidation of these mechanisms opens the door for future clinical applications targeting this protein. Additional studies are needed to address important questions including the relationship between extracellular Nampt and carcinogenesis.
烟酰胺磷酸核糖转移酶(Nampt)是催化哺乳动物烟酰胺腺嘌呤二核苷酸(NAD)补救途径第一步的限速酶。异常的NAD代谢与致癌信号转导相关,提示Nampt在肿瘤发生和转移中起关键作用。此外,Nampt可分泌到细胞外,这种细胞外形式的Nampt(eNampt)因其细胞因子活性可诱导炎症和血管生成,这也可能参与致癌过程。
本文综述了Nampt在致癌作用研究方面的最新进展,特别强调了Nampt抑制剂及未来临床应用,包括癌症诊断、预后和治疗。专家评论:Nampt不仅维持细胞代谢平衡,还对致癌作用的多个方面有深远影响。因此,阐明这些机制为未来针对该蛋白的临床应用打开了大门。还需要进一步研究来解决重要问题,包括细胞外Nampt与致癌作用之间的关系。