An indispensable role of CPT-1a to survive cancer cells during energy stress through rewiring cancer metabolism

In this study, we investigated the functional roles of fatty acid oxidation key enzyme carnitine palmitoyl transferase 1a (CPT-1a), during the metabolic programming of pancreatic ductal adenocarcinoma (PDAC) cells induced by glucose deprivation. Knockdown of CPT-1a decreased the intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) generation, increased reactive oxygen species (ROS) production, and induced sensitivity to glucose deprivation, whereas upregulation of CPT-1a increased the intracellular ATP required for cell survival. Further investigation showed that CPT-1a inhibitor etomoxir (ETO) can restore the sensitivity of PDAC cells to gemcitabine and regress xenograft tumors in vivo. Finally, overexpression of CPT-1a expression is associated with chemoresistance in tumor specimens. Our data suggest that CPT-1a plays a key role in reprogramming cancer metabolism to escape from energy stress.
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research