Abstract
Unlike normal cells, cancer cells are recently identified to rely on aerobic glycolysis for energy production called the Warburg effect. Several attempts are being made to target this metabolic reprogramming pathway in treating cancers; however, the successful rate is very limited. 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.
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This study was supported by the grant from the National Natural Science Foundation of China (No. 81401412).
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All the subjects signed informed consent documents. The protocol for this study was in accordance with the Declaration of Helsinki and its subsequent revisions, and it was approved by the Institutional Review Boards of the Tianjin Medical University Cancer Institute & Hospital.
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Luo, J., Hong, Y., Tao, X. et al. An indispensable role of CPT-1a to survive cancer cells during energy stress through rewiring cancer metabolism. Tumor Biol. 37, 15795–15804 (2016). https://doi.org/10.1007/s13277-016-5382-6
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DOI: https://doi.org/10.1007/s13277-016-5382-6