A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma - PubMed
2 days ago
- #HK1
- #TGF-β1
- #Hepatocellular Carcinoma
- Hepatocellular carcinoma (HCC) progression is influenced by a unique intercellular feedforward loop involving HK1 and TGF-β1.
- Hepatic stellate cells (HSCs) secrete hexokinase 1 (HK1) via large extracellular vesicles (lEVs), which are taken up by HCC cells to boost glucose metabolism.
- Enhanced glucose metabolism in HCC cells reciprocally activates HSCs, creating a pro-tumourigenic fibrotic microenvironment.
- HK1 accelerates the hexosamine biosynthesis pathway, promoting N-glycosylation and secretion of TGF-β1 from HCC cells, which further activates HSCs.
- Disrupting this feedforward loop significantly inhibits HCC progression, suggesting a potential therapeutic strategy.