title: An indispensable role of CPT-1a to survive cancer cells during energy stress through rewiring cancer metabolism.
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.
authors.affiliation: The Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.|Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.|Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, China.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Tao
authors.affiliation: The Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.|Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL, 33612, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Wei
authors.affiliation: The Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. qli@tmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
keywords: CPT-1a; Energy stress; Fatty acid metabolism; Warburg effect