ArticleMolecular & cellular proteomics : MCP2018
Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- NAMPT Deficiency Promotes Endothelial-Mesenchymal Transition by Inhibiting Energy Metabolism and Lysosomal Acidification in Late-Onset Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- Phosphosite-centric regulatory network of ATAD2 and its involvement in transcriptional networks.Molecular genetics and genomics : MGG · 2026Article
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Decoding NAD+ Metabolism in COVID-19: Implications for Immune Modulation and Therapy.Vaccines · 2024Review
- Disruption of perinatal myeloid niches impacts the aging clock of pancreatic β cells.iScience · 2024Article
- Targeting HOXA11-AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo.Journal of cellular and molecular medicine · 2024Article
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
- Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice.Nutrients · 2023Article
- NicotinamideACS omega · 2022Article
- Duodenal Metabolic Profile Changes in Heat-Stressed Broilers.Animals : an open access journal from MDPI · 2022Article
- Regulation of epithelial-mesenchymal transition by protein lysine acetylation.Cell communication and signaling : CCS · 2022Review
- The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.American journal of physiology. Cell physiology · 2022Review
- The Epithelial-Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression.International journal of molecular sciences · 2022Review
- Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.Cell death and differentiation · 2021Review
- Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer.International journal of molecular sciences · 2021Review
- NADSignal transduction and targeted therapy · 2020Review
- Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations.World journal of gastroenterology · 2020Review
- Effects of Epigallocatechin Gallate (EGCG) on Urinary Bladder Urothelial Carcinoma-Next-Generation Sequencing and Bioinformatics Approaches.Medicina (Kaunas, Lithuania) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinamide adenine dinucleotide (NAD) plays an essential role in all aspects of human life. NAD levels decrease as humans age, and supplementation with NAD precursors plays a protective role against aging and associated disease. Less is known about the effects of decreased NAD on cellular processes, which is the basis for understanding the relationship between cellular NAD levels and aging-associated disease. In the present study, cellular NAD levels were decreased by overexpression of CD38, a NAD hydrolase, or by treating cells with FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Quantitative proteomics revealed that declining NAD levels downregulated proteins associated with primary metabolism and suppressed cell growth in culture and nude mice. Decreased glutathione synthesis caused a 4-fold increase in cellular reactive oxygen species levels, and more importantly upregulated proteins related to movement and adhesion. In turn, this significantly changed cell morphology and caused cells to undergo epithelial to mesenchymal transition (EMT). Secretomic analysis also showed that decreased NAD triggered interleukin-6 and transforming growth factor beta (TGFβ) secretion, which activated integrin-β-catenin, TGFβ-MAPK, and inflammation signaling pathways to sustain the signaling required for EMT. We further revealed that decreased NAD inactivated sirtuin 1, resulting in increased signal transducer and activator of transcription 3 (STAT3) acetylation and phosphorylation, and STAT3 activation. Repletion of nicotinamide or nicotinic acid inactivated STAT3 and reversed EMT, as did STAT3 inhibition. Taken together, these results indicate that decreased NAD activates multiple signaling pathways to promote EMT and suggests that age-dependent decreases in NAD may contribute to tumor progression. Consequently, repletion of NAD precursors has potential benefits for inhibiting cancer progression.
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Registered trials
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