FOXO1 functions in the regulation of nicotinamide phosphoribosyltransferase (Nampt) expression

Jeong, Bora; Park, Jeong Woo; Kim, Jae Geun; Lee, Byung Ju

doi:10.1016/j.bbrc.2019.02.069

Cited by 10 publications

(8 citation statements)

References 27 publications

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“…From a clinical perspective, co-targeting NAMPT with these pathways may be a beneficial strategy. In some cases, oncogenic factors regulate expression and activity of NAMPT, such as in Ewing sarcoma, where the oncogenic transcription factor EWS-FLI1 has been shown to regulate NAMPT expression (49) and in breast cancer, where FOXO1, a tumor suppressor, negatively regulates the expression of NAMPT while AKT positively regulates it (117). In other cases, NAMPT regulates the activity of oncogenic signaling pathways.…”

Section: Oncogenic Signalingmentioning

confidence: 99%

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Heske

2020

Front. Oncol.

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Tumor cells have increased requirements for NAD +. Thus, many cancers exhibit an increased reliance on NAD + production pathways. This dependence may be exploited therapeutically through pharmacological targeting of NAMPT, the rate-limiting enzyme in the NAD + salvage pathway. Despite promising preclinical data using NAMPT inhibitors in cancer models, early NAMPT inhibitors showed limited efficacy in several early phase clinical trials, necessitating the identification of strategies, such as drug combinations, to enhance their efficacy. While the effect of NAMPT inhibitors on impairment of energy metabolism in cancer cells has been well-described, more recent insights have uncovered a number of additional targetable cellular processes that are impacted by inhibition of NAMPT. These include sirtuin function, DNA repair machinery, redox homeostasis, molecular signaling, cellular stemness, and immune processes. This review highlights the recent findings describing the effects of NAMPT inhibitors on the non-metabolic functions of malignant cells, with a focus on how this information can be leveraged clinically. Combining NAMPT inhibitors with other therapies that target NAD +-dependent processes or selecting tumors with specific vulnerabilities that can be co-targeted with NAMPT inhibitors may represent opportunities to exploit the multiple functions of this enzyme for greater therapeutic benefit.

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Section: Oncogenic Signalingmentioning

confidence: 99%

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Heske

2020

Front. Oncol.

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“…Our current research reported that the regulation of lipid deposition by insulin in goose liver cells was mediated by the PI3K-Akt-mTOR signaling pathway (Han et al, 2015). A current study demonstrated that nicotinamide phosphoribosyltransferase (Nampt) is a transcriptional target of FoxO1 that is under control of the insulin-PI3K-Akt pathway and the stimulatory effect of insulin signaling pathways on the Nampt gene expression is largely due to inhibitory action on FoxO1 (Jeong et al, 2019). However, whether FoxO1 regulated the cell proliferation and lipid metabolism mediated by insulin in reverse is unclear.…”

Section: Introductionmentioning

confidence: 85%

Forkhead box protein O1 (FoxO1) regulates lipids metabolism and cell proliferation mediated by insulin and PI3K-Akt-mTOR pathway in goose primary hepatocytes

Wei¹,

Han²,

Ye³

et al. 2022

Biocell

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In order to explore the role of forkhead box protein O1 (FoxO1) in the lipid metabolism and cell proliferation, goose primary hepatocytes were isolated and incubated with insulin or PI3K-Akt-mTOR pathway dual inhibitor NVP-BEZ235, and then transfected with FoxO1 interference plasmid. The related parameters of lipid metabolism and cell proliferation were measured. The results firstly showed that FoxO1 interference increased the intracellular TG and lipids concentration (P < 0.05); and increased the proliferative index (PI), cell DNA synthesis, protein expression of Cyclin D1 in goose primary hepatocytes (P < 0.05). Secondly, the co-treatment of insulin and FoxO1 interference increased the mRNA level and protein content of Cyclin D1 (P < 0.05); however, there was no significant difference between the insulin treatment and the co-treatment of insulin and miR-FoxO1 interference in the intracellular TG and lipids concentration and PI (P > 0.05). Lastly, the decrease of intracellular TG and lipids concentration and PI induced by NVP-BEZ235 was up-regulated by FoxO1 interference significantly (P < 0.05). In summary, FoxO1 could regulate the lipids metabolism and cell proliferation mediated by PI3K-Akt-mTOR signaling pathway in goose primary hepatocytes. Further investigations are required to highlight the potential role of FoxO1 in the lipid metabolism and cell proliferation mediated by insulin in goose primary hepatocyte.

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“…In a latest study, a new AS-lncRNA RP11-22N19.2, which was transcribed from the antisense strand of NAMPT, has been reported to enhance the transcriptional activity of NAMPT in triple negative breast cancer (8). In addition, the transcription of NAMPT gene can be directly regulated by FOXO1 in breast cancer (31). Mutant IDH1 can also downregulate NAPRT in glioma (32).…”

Section: Discussionmentioning

confidence: 99%

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

Lei

Mao

et al. 2019

Front. Oncol.

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Nicotinamide adenine dinucleotide (NAD) is a profoundly important cofactor in redox reactions. Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are key enzymes for NAD salvage biosynthesis pathway, which reciprocally synthesize NAD to supply the main source of NAD biosythesis. However, the prognostic value of NAMPT and NAPRT in colorectal cancer (CRC) remains largely unknown. Our present study detected NAMPT and NAPRT protein expression in cancer and adjacent tissues from 261 CRC using immunohistochemical staining. We found that high expression of NAMPT or NAPRT was associated with vascular invasion, invasion depth and advanced TNM stage in CRC. High expression of NAMPT or NAPRT predicts short overall survival and disease-free survival time in CRC patients, which were further confirmed by public datasets. Furthermore, positive correlation between expression of NAMPT and NAPRT was revealed in CRC tissues and cell lines. NAPRT high /NAMPT high patients tended to have the shortest survival time. Using the TCGA RNA-sequencing data, we showed that gene amplification, mutation, and methylation of NAPRT are more common than NAMPT. On the other hand, NAMPT gene might be targeted by more miRNAs. Finally, genes that are correlated with NAPRT or NAMPT are enriched in different pathways. In conclusion, we found that high expression of NAMPT or NAPRT predicts poor prognosis of CRC patients, but the regulatory mechanism might be distinct from each other.

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FOXO1 functions in the regulation of nicotinamide phosphoribosyltransferase (Nampt) expression

Cited by 10 publications

References 27 publications

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Forkhead box protein O1 (FoxO1) regulates lipids metabolism and cell proliferation mediated by insulin and PI3K-Akt-mTOR pathway in goose primary hepatocytes

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

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