Glutamine-mediated epigenetic regulation of cFLIP underlies resistance to TRAIL in pancreatic cancer

Experimental & Molecular Medicine, Published online: 30 April 2024; doi:10.1038/s12276-024-01231-0Pancreatic ductal adenocarcinoma (PDAC), a severe form of pancreatic cancer with a low survival rate, was the focus of this study. The aim was to understand why PDAC is resistant to TRAIL-induced programmed cell death (apoptosis). The study found that PDAC cells need glutamine (a type of amino acid) to be resistant to TRAIL-induced apoptosis. Without glutamine, these cells are more likely to undergo TRAIL-induced apoptosis due to a decrease in a protein called cFLIP. This protein’s regulation involves a process with glutamine-derived alpha-ketoglutarate (aKG), a chemical compound. The study also discovered that an enzyme called KDM4C helps regulate cFLIP. The results suggest that focusing on glutamine metabolism could be a potential TRAIL-based therapy for PDAC.
Source: Experimental and Molecular Medicine - Category: Molecular Biology Authors: Source Type: research