Nicotinamide phosphoribosyl transferase regulates cell growth via the Sirt1/P53 signaling pathway and is a prognosis marker in colorectal cancer

• Published in: Journal of cellular physiology Vol. 234; no. 4; pp. 4385 - 4395
• Main Authors: Pan, Jing‐hua, Zhou, Hong, Zhu, Sheng‐Bin, Huang, Jin‐Lian, Zhao, Xiao‐Xu, Ding, Hui, Qin, Li, Pan, Yun‐Long
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: Acrylamides - pharmacology; Adenine; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Caspase; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell growth; Cell Proliferation - drug effects; Colon; Colorectal cancer; colorectal cancer (CRC); Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Cyclin D1; Cytokines - antagonists & inhibitors; Cytokines - genetics; Cytokines - metabolism; Enzyme Inhibitors - pharmacology; Enzymes; Female; FK866; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycolysis; Growth inhibition; HCT116 Cells; Humans; Localization; Male; Malignancy; Medical prognosis; Middle Aged; Nicotinamide; nicotinamide phosphoribosyl transferase (NAMPT); Nicotinamide Phosphoribosyltransferase - antagonists & inhibitors; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; p53 Protein; Piperidines - pharmacology; Proteins; Rectum; Regulatory mechanisms (biology); Signal Transduction; Signaling; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Survival; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; apoptosis; colorectal cancer (CRC); cell cycle; FK866; nicotinamide phosphoribosyl transferase (NAMPT)
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27228

Colorectal cancer (CRC) is the third most common malignancy, and the metabolic properties of CRC cells include enhanced aerobic glycolysis (the Warburg effect). Nicotinamide phosphoribosyl transferase (NAMPT) is one of the crucial enzymes that regulate the activity of nicotinamide adenine dinucleodinucleotide dependent enzymes. Targeting NAMPT is a potential method of CRC therapy. Nevertheless, the underlying clinical implications and regulatory mechanisms of NAMPT in CRC remain unclear. In this study, we showed that NAMPT protein expression was increased in subjects with rectal localization compared with those with colon localization, and NAMPT was a poor prognostic marker for the overall survival rate in patients with CRC. In addition, the NAMPT inhibitor FK866 or lentivirus‐mediated silencing induced CRC cell growth inhibition. Mechanistically, NAMPT regulated Sirt1 and P53 expression and induced G0/G1 cell cycle arrest, along with the upregulation of downstream p21 and downregulation of cyclin D1, cyclin E1, and cyclin E2 expression. FK866 administration or knockdown of NAMPT induced CRC cell apoptosis via upregulation of caspase‐3. In conclusion, NAMPT regulated Sirt1/P53 signaling during CRC cell growth and warrants further investigation for clinical administration in CRC. 1. Overexpression of nicotinamide phosphoribosyl transferase (NAMPT) was detected in colorectal cancer (CRC) tissue compared to normal colorectal samples. 2. NAMPT inhibitor FK866 or lentivirus‐mediated silencing induced CRC cell growth inhibition. 3. NAMPT regulated Sirt1/P53 signaling during CRC cell growth.