Warburg效应（异常糖酵解）促进肿瘤生长。我们上一个国家自然基金证实TAZ与肺癌生长转移有关。但TAZ在Wargburg效应中的作用不详。我们行RNA-seq和KEGG通路富集分析，首次发现TAZ与肺癌糖酵解有关。免疫共沉淀结合质谱分析筛选出与TAZ作用的组蛋白乙酰转移酶（HAT）p300和pCAF。那么，TAZ的上游调控因子是什么呢？我们已证实Ski低表达促进肿瘤生长、增加糖酵解，同时TAZ表达上调。由此我们提出TAZ调控肺癌Warburg效应的新机制：Ski磷酸化调控TAZ；TAZ通过p300和pCAF介导的组蛋白乙酰化修饰促进糖酵解基因转录和肺癌生长。我们拟采用ChIP、Re-ChIP、His pull-down、GST pull-down、PCR定点突变、体外磷酸化等技术，旨在证实Ski/TAZ信号轴通过HAT促进糖酵解基因转录调控。本课题将为寻找靶向糖代谢的抗癌药提供新途径。

Warburg effect (abnormal glycolysis) promotes tumor growth. Our National Natural Fund has confirmed that TAZ is associated with the growth and metastasis of lung cancer. However, the role of TAZ in Wargburg effect is unknown. We performed RNA-seq and KEGG pathway enrichment analysis and found for the first time that TAZ was associated with glycolysis in lung cancer. Histone acetyltransferase (HAT) P300 and pCAF were screened by immunoprecipitation combined with mass spectrometry. So what are the upstream regulators of TAZ? We have confirmed that low Ski expression promotes tumor growth, increases glycolysis, and up-regulates TAZ expression. Therefore, we propose a new mechanism for TAZ to regulate the Warburg effect of lung cancer: Ski phosphorylation regulates TAZ; TAZ promotes glycolysis gene transcription and lung cancer growth through P300 and pCAF-mediated histone acetylation. We intend to use ChIP, Re-ChIP, His pull-down, GST pull-down, PCR site-directed mutagenesis and in vitro phosphorylation to confirm the mechanism of Ski/TAZ signaling promoting glycolysis gene transcription through p300/pCAF. This project will provide a new way for anticancer drugs targeting sugar metabolism.