CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

作     者：Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Ming Shao;Qingfei Pan;Haiyan Tan;Jing Wu;Ha Won Lee;Andrew D.Huber;William C.Wright;Ji-Hoon Cho;Jiyang Yu;Junmin Peng;Taosheng Chen

作者机构：Department of Chemical Biology and TherapeuticsSt.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational BiologySt.Jude Children's Research HospitalMemphisTN 38105USA Center for Proteomics and MetabolomicsSt.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural BiologySt.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental NeurobiologySt.Jude Children's Research HospitalMemphisTN 38105USA 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第4期

页      面：381-399页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM118041 

主　　题：Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP 

摘      要：CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.