Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma.

ABSTRACT: Tumour-derived small extracellular vesicles (sEV) are critical mediators within the tumour microenvironment (TME) and are known to regulate various metabolic pathways. In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC-derived sEV (HCC-sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Our study demonstrates that sEV-NAMPT enhances glycolysis, tumorigenesis, and metastasis in HCC. Specifically, sEV-NAMPT activates the NF-κB transcription factor through toll-like receptor 4 (TLR4), leading to elevated SLC27A4 expression. SLC27A4 functions primarily as a long-chain fatty acid transporter and acyl-CoA synthetase. Lipidomic and metabolomic a

SUBMITTER: Yeung CLS 

PROVIDER: S-EPMC12000932 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature