肝细胞癌（HCC）是我国常见的恶性肿瘤之一。我们前期证实HSP90是一个独立的HCC患者预后标记物，HSP90具有促进HCC细胞增殖和凋亡的作用，但是具体机制不清；PKM2在肿瘤中调控肿瘤代谢，但是其在肿瘤非代谢途径中的具体分子机制仍不明确。课题组前期研究发现HCC组织中HSP90与PKM2蛋白表达正相关，HCC细胞中HSP90正向调控PKM2蛋白，免疫共沉淀发现HSP90与PKM2蛋白存在相互作用，进一步质谱分析发现过表达HSP90可以使PKM2发生磷酸化，本研究是个既往研究的深入，拟通过体内外实验证明HSP90通过磷酸化PKM2发挥其致癌作用，进而通过基因突变等技术探讨HSP90磷酸化PKM2的具体分子机制，并明确在这一调控过程中是否有其他蛋白如GSK3β的参与。本项目旨在阐明HSP90调控PKM2在肝细胞癌中的具体作用机制，为临床上开发新的靶向治疗药物和预后标志物提供依据。

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in China. Since our previous study indicates that HSP90 is an independent prognostic marker in HCC and HSP90 promotes cell proliferation and induces apoptosis in HCC cells, but the mechanisms is still unclear. The abnormal activation and accumulation of PKM2 protein in the tumor is a key factor for Tumor metabolism , but the mechanisms of PKM2 in non-metabolic pathway is still unknown. Our previous research shown that HSP90 was positively correlated with HSP90 protein in HCC tissues and HSP90 regulated the expression of PKM2 protein in HCC cells. We found that there was interaction between HSP90 and PKM2 by using co-immunoprecipitation and phosphorylation sites recognized in PKM2 protein when overexpression of HSP90 by using mass spectrometric analysis. In the present project, we try to determine whether HSP90 functions as a oncogene by phosphorylation PKM2 protein. Furthermore, we attempt to verify the mechanisms involved in phosphorylation and regulation of PKM2 protein by HSP90 through gene mutagenesis, and find out if there are any other proteins, such as GSK3, taking part in this process. The aim of this project is to investigate the molecular mechanisms of HSP90 regulates PKM2 protein in HCC , in order to provide the scientific basis to exploit novel targeting agents and predictive biomarkers for HCC clinically.