PIM2通过磷酸化AMPKα1调控肿瘤细胞糖代谢的分子机制研究

肿瘤发生是一个非常复杂的过程，是由多种因素和多条信号通路的异常促成的，其中糖代谢通量异常增加就是一个非常重要的因素。腺苷酸活化蛋白激酶（AMPK）信号通路处在糖代谢的核心位置，起到代谢阀门的作用，但是调控AMPK通路的分子机制尚未明确。本课题通过一系列生化手段研究莫罗尼小鼠白血病病毒插入蛋白2（PIM2）与AMPKα1的相互作用，通过体外磷酸化实验和质谱仪研究PIM2磷酸化AMPKα1，研究PIM2磷酸化AMPKα1后增强肿瘤细胞糖酵解、侵袭和增殖，研究该磷酸化修饰降低线粒体呼吸功能和对药物的化疗敏感性。从而阐述PIM2调控AMPK信号通路的分子机制，为临床靶向PIM2和AMPKα1合成药物治疗肿瘤奠定理论基础。

Tumorigenesis is a very complicated process, which is led by many factors and many signal pathways. Glucose metabolic reprogramming plays an important role in regulating tumorigenesis. AMP-activated protein kinase (AMPK) pathway is a glucose metabolic checkpoint, but the mechanism of regulating AMPK pathway is still unclear. Here, we use multiple biochemical approaches to study the interaction between proviral insertion in murine lymphomas 2 (PIM2) and AMPKα1. We use the in vitro assays and mass spectrum to study PIM2 phosphorylates AMPKα1. We research this phosphorylation increases glycolysis, cell invasion and proliferation, but decreases mitochondrial respiration and chemotherapy sensitivity. So we describe a new molecular mechanism of PIM2-dependent phosphorylation of AMPKα1, highlighting PIM2 and AMPKα1 as potential therapeutic targets for producing new drugs.