活跃的脂肪酸合成与肿瘤发生发展密切相关，是肿瘤代谢重组的重要表现之一，成为近年来的研究热点。SREBP1转录因子是调节脂肪酸合成的关键因子，而肿瘤细胞如何调控SREBP1以实现脂质代谢重组的机制尚不完全清楚。本项目前期工作发现：CDK8在伙伴蛋白CNC的辅助下（CDK8/CNC复合体），通过磷酸化SREBP1的402位苏氨酸调控SREBP1转录因子活性，且CDK8/CNC的蛋白、磷酸化水平与生长因子等信号激活的mTORC1功能密切相关。本研究拟评估mTORC1对CDK8/CNC的调节作用，揭示mTROC1磷酸化调节CDK8/CNC的分子机制，并阐明该磷酸化机制与肿瘤发生发展的关系。研究以CDK8/CNC的转录后修饰机制为切入点，阐述生长因子或激素等信号通过mTORC1-CDK8/CNC-SREBP1信号轴调控脂肪酸合成的理论模型，以期完善肿瘤脂质代谢的重组机制，且为肿瘤的诊治提供新思路。

Accumulating evidences have revealed that tumorigenesis is associated with de novo lipogenesis, which is mainly regulated by transcription factor SREBP1. Our previous study indicated that CDK8/CNC regulated lipogenesis via phosphorylating 402 threonine of SREBP1; the level of CDK8/CNC was regulated by growth factors or hormone; protein or phosphorylation level of CDK8/CMC was related the activity of mTORC1. Therefore, our research tried to understand the underlying mechanisms of mTORC1-mediated lipogenesis via phosphorylating CDK8/CNC. The in vivo model of mTORC1; the stability and integrity assay of CDK8/CNC complex; the phosphorylation assay and de novo lipogenesis assay were applied in this study. We focused our research on posttranscriptional regulation of CDK8/CNC to elucidate the role of mTORC1-CDK8/CNC-SREBP1 signaling axis in lipid metabolism of cancer. Our research would provide evidence for deeply understanding the role of metabolic reprogramming in cancer.