肿瘤细胞的代谢模式有别于正常体细胞，通常伴有糖、脂代谢的异常活跃。靶向糖、脂代谢关键基因诊断和治疗肿瘤成为了目前的研究热点。葡萄糖是肿瘤脂肪合成的重要碳源，肿瘤细胞则通过关键转录因子 SREBP 上调促进摄取碳源合成脂肪酸，从而促进肿瘤细胞的增殖，但糖代谢与脂肪酸代谢之间的关系和之间的调节机制目前仍不明确。申请人前期研究发现PKM2可以磷酸化GSK3β而导致GSK3β降解，而GSK3β是脂肪代谢关键基因 SREBP1的重要的上游激酶。因此推测PKM2 -GSK3β-SREBP1存在信号传导通路，PKM2可以通过磷酸化GSK3β的方式调控SREBP1从而导致肿瘤细胞脂质代谢重组。为了验证该假说本课题拟以蛋白质相互作用为研究核心，通过蛋白-细胞-动物-人体组织标本水平多角度多层次揭示PKM2对脂肪调控的分子机制。该研究将阐明肿瘤细胞糖代谢与脂肪代谢之间的关系，并为肿瘤的诊治提供新的靶点。

Glucose metabolism and lipid metabolism are active in most of tumor cell.There is continued interest in the key enzymes of glucose metabolism and lipid metabolism to target diagnosis and treatment of tumor. Glucose is an important carbon source of fatty acid synthesis. Fatty acid synthesis is regulated by the core transcrip SREBP. However, the mechanisms of tumor cells persistent activating glucose metabolism and lipid metabolism are not fully understood. Our previous researchindicated that pkm2 could regulate lipogenesis and PKM2 activity is related with the phosphorylation level of GSK3β. We hypothesized that PKM2-GSK3β-SREBP1 signaling pathway could stimulate de novo lipogenesis. Our study will provide the new therapy and diagnosis target for cancer.