非小细胞肺癌中氨基己糖合成途径通过SCA10正向调控谷氨酰胺代谢.pdfVIP

Abstract ABSTRACT Glycometabolism and glutaminolysis were the tw primary carbon sources and nitrogen sourcesforNSCLC,whichwererearranged comparedwithnormal cells.Itwas reportedthathexosaminebiosyntheticpathway(HBP)ishighlyactivatedinNSCLCcells which are als addicted t glutamine. HBP and glutamine play significant roles in the development andprogression ofNSCLC,but theprecise mechanism isnot clear.Based on these, we used GAC as a bait t screen the interactors using the yeast tw -hybrid system. One of them was SpinocerbellarAtaxin type 10(SCA10),which may be as an adaptor protein recruited OGT and GAC. Biochemistry experiments were showed that OGT could stabilized GAC protein. Thus, a novel metabolic pathway was found in NSCLC that HBP activates OGT t stabilize GAC with the help of adaptor protein SCA10, positively regulate glutaminolysis.We demonstrated that SCA10 couples glycometabolism t glutaminolysis for the first time. Therefore, The SCA10 may be a noveldrugtargetforclinicaltherapyofNSCLC. KeyWords:NSCLC;HBP;O-GlcNAc;GAC;SCA10 III 目录 目 录 第一章：绪论1 1.1 非小细胞肺癌的研究现状和意义1 1.2 肿瘤细胞中代谢重排现象的研究2 1.2.1肿瘤细胞代谢与Warbury效应3 1.2.2 肿瘤细胞中谷氨酰胺代谢的研究4 1.3 10 SCA10 6 脊髓小脑共济失调蛋白 （ ）的研究进展 1.4氨基己糖合成途径（HBP）在肿瘤代谢中的研究7 1.5 代谢的调控研究在肿瘤的治疗中的意义9 1.6 本课题研究的目的和意义10 第二章：材料和方法11 2.1材料11 2.2 实验方法11 第三章 实验结果16 3.1NSCLC 的生长依赖于谷氨酰胺代谢通路16 3.1.1NSCLC 的生长依赖于谷氨酰胺16 3.1.2NSCLC GAC 16 中 扮演重要角色 3.1.3NSCLC表型依赖于GAC18 3.2GAC SCA10 20 的相互作用蛋白 支架蛋白 的筛