ArticleCell death and differentiation2016
The NAD(+) salvage pathway modulates cancer cell viability via p73.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 62 citations in OpenAlex.
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- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- Inhibition of TRAF3IP2 Modulates NAMPT and NAD Metabolism in Glioblastoma.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- The adipokines in oral cancer pathogenesis and its potential as a new therapeutic approach.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
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- Homeostatic regulation of NAD(H) and NADP(H) in cells.Genes & diseases · 2024Review
- Plasma-activated medium exerts tumor-specific inhibitory effect on hepatocellular carcinoma via disruption of the salvage pathway.Journal of clinical biochemistry and nutrition · 2024Article
- Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases.Biochemistry and biophysics reports · 2024Review
- The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.Cancer science · 2023Article
- Glycolysis-related lncRNA TMEM105 upregulates LDHA to facilitate breast cancer liver metastasis via sponging miR-1208.Cell death & disease · 2023Article
- Review
- NAMPT-targeting PROTAC promotes antitumor immunityActa pharmaceutica Sinica. B · 2022Article
- Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.Cancer discovery · 2022Article
- Review
- Mutational Pattern Induced by 5-Fluorouracil and Oxaliplatin in the Gut Microbiome.Frontiers in microbiology · 2022Article
- Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer.Frontiers in endocrinology · 2022Article
- NAMPT Inhibition Induces Neuroblastoma Cell Death and Blocks Tumor Growth.Frontiers in oncology · 2022Article
- Visfatin Polymorphisms, Lifestyle Risk Factors and Risk of Oral Squamous Cell Carcinoma in a Cohort of Taiwanese Males.International journal of medical sciences · 2022Article
- Optical Redox Imaging of Treatment Responses to Nampt Inhibition and Combination Therapy in Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2021Article
Corrections and comments
- Expression of concern
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The involvement of the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway in cancer cell survival is poorly understood. Here we show that the NAD(+) salvage pathway modulates cancer cell survival through the rarely mutated tumour suppressor p73. Our data show that pharmacological inhibition or knockdown of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD(+) salvage pathway, enhances autophagy and decreases survival of cancer cells in a p53-independent manner. Such NAMPT inhibition stabilizes p73 independently of p53 through increased acetylation and decreased ubiquitination, resulting in enhanced autophagy and cell death. These effects of NAMPT inhibition can be effectively reversed using nicotinamide mononucleotide (NMN), the enzymatic product of NAMPT. Similarly, knockdown of p73 also decreases NAMPT inhibition-induced autophagy and cell death, whereas overexpression of p73 alone enhances these effects. We show that the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) harbour significantly higher levels of NAMPT and lower levels of p73 than does the normal cell line (MCF-10A), and that NAMPT inhibition is cytotoxic exclusively to the cancer cells. Furthermore, data from 176 breast cancer patients demonstrate that higher levels of NAMPT and lower levels of p73 correlate with poorer patient survival, and that high-grade tumours have significantly higher NAMPT/p73 mRNA ratios. Therefore, the inverse relationship between NAMPT and p73 demonstrable in vitro is also reflected from the clinical data. Taken together, our studies reveal a new NAMPT-p73 nexus that likely has important implications for cancer diagnosis, prognosis and treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.