NAMPT and NAPRT, Key Enzymes in NAD Salvage Synthesis Pathway, Are of Negative Prognostic Value in Colorectal Cancer

Li, Xiao qin; Lei, Jing; Mao, Ling; Wang, Qing Liang; Xu, Feng; Tao, Ran; Zhou, Zhi; He, Song

doi:10.3389/fonc.2019.00736

Cited by 38 publications

(47 citation statements)

References 34 publications

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“…In ovarian, 216 prostate and pancreatic cancers, NAPRT has been found upregulated just like NAMPT gene. 193 , 217 While in glioblastoma, neuroblastomas, 218 chondrosarcoma, 219 gastric cancer, 220 leukemia 193 , and colorectal cancer, 221 NAPRT has been found downregulated.…”

Section: Naprt In Tumorsmentioning

confidence: 97%

NAD+ metabolism, stemness, the immune response, and cancer

Navas

Carnero

2021

Sig Transduct Target Ther

276

218

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NAD+ was discovered during yeast fermentation, and since its discovery, its important roles in redox metabolism, aging, and longevity, the immune system and DNA repair have been highlighted. A deregulation of the NAD+ levels has been associated with metabolic diseases and aging-related diseases, including neurodegeneration, defective immune responses, and cancer. NAD+ acts as a cofactor through its interplay with NADH, playing an essential role in many enzymatic reactions of energy metabolism, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, and the TCA cycle. NAD+ also plays a role in deacetylation by sirtuins and ADP ribosylation during DNA damage/repair by PARP proteins. Finally, different NAD hydrolase proteins also consume NAD+ while converting it into ADP-ribose or its cyclic counterpart. Some of these proteins, such as CD38, seem to be extensively involved in the immune response. Since NAD cannot be taken directly from food, NAD metabolism is essential, and NAMPT is the key enzyme recovering NAD from nicotinamide and generating most of the NAD cellular pools. Because of the complex network of pathways in which NAD+ is essential, the important role of NAD+ and its key generating enzyme, NAMPT, in cancer is understandable. In the present work, we review the role of NAD+ and NAMPT in the ways that they may influence cancer metabolism, the immune system, stemness, aging, and cancer. Finally, we review some ongoing research on therapeutic approaches.

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Section: Naprt In Tumorsmentioning

confidence: 97%

NAD+ metabolism, stemness, the immune response, and cancer

Navas

Carnero

2021

Sig Transduct Target Ther

276

218

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“…410 High expression of NAMPT or NAPRT is associated with tumor progression, invasion, and drug resistance. [411][412][413][414] This effect is mediated by NAD + -dependent PARPs and SIRT1. [415][416][417] SIRT6 induces the NAMPT activity to increase NAD + content, thereby preventing oxidative damage.…”

Section: Abnormal Nad + Metabolism In the Pathophysiological Conditionmentioning

confidence: 99%

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

Xie

Zhang

Gao

et al. 2020

Sig Transduct Target Ther

559

383

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Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

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“…Likewise, NAPRT protein is differentially expressed between cell lines, with markedly decreased expression in carcinoma cell lines MKN28 (gastric), 786-O (renal), HCT116 (colorectal), and in all leukemia cell lines tested (HL-60, NB4, and ML2) (88). Another paper highlighted a role for NAPRT, together with NAMPT, as negative prognostic marker in colorectal cancer, based on TCGA RNAsequencing data and protein tissue array (180). In a recent work the overexpression of NAPRT in ovarian cancer, correlated with a BRCAness gene expression signature.…”

Section: Nampt and Naprt In Tumorsmentioning

confidence: 99%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are two intracellular enzymes that catalyze the first step in the biosynthesis of NAD from nicotinamide and nicotinic acid, respectively. By fine tuning intracellular NAD levels, they are involved in the regulation/reprogramming of cellular metabolism and in the control of the activity of NAD-dependent enzymes, including sirtuins, PARPs, and NADases. However, during evolution they both acquired novel functions as extracellular endogenous mediators of inflammation. It is well-known that cellular stress and/or damage induce release in the extracellular milieu of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune functions through binding pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and activate inflammatory responses. Increasing evidence suggests that extracellular (e)NAMPT and eNAPRT are novel soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported in several metabolic and inflammatory disorders, including obesity, diabetes, and cancer, while eNAPRT is emerging as a biomarker of sepsis and septic shock. This review will discuss available data concerning the dual role of this unique family of enzymes.

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NAMPT and NAPRT, Key Enzymes in NAD Salvage Synthesis Pathway, Are of Negative Prognostic Value in Colorectal Cancer

Cited by 38 publications

References 34 publications

NAD+ metabolism, stemness, the immune response, and cancer

NAD+ metabolism, stemness, the immune response, and cancer

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

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