YAP-p53信号通路影响肝细胞肝癌发生的相关机制研究

80%的肝细胞癌（HCC）伴有肝硬化，而FDA获准的唯一靶向治疗药物索拉菲尼在肝硬化条件下易产生抗药性，这成为HCC靶向治疗的瓶颈。本课题从HCC肝硬化的YAP-p53蛋白微调节通路入手，计划探索肿瘤微环境的改变、基质硬度改变以及力学因素干扰所导致的YAP-p53等信号通路的改变，进而发现对索拉菲尼抗药性的影响，发掘HCC治疗的新靶点。此项目符合国内外“精准医疗”发展理念，具有重要转化医学价值。

80% of hepatocellular carcinoma (HCC) is accompanied by liver cirrhosis. Sorafenib, the only FDA approved targeted drug for HCC is prone to resistance in the case of cirrhosis, which is the bottleneck for HCC targeted therapies. This project starts from micro-regulation of YAP-p53 pathway in liver cells, in ordering to explore how would the YAP-p53 signaling pathway response under the changes of the tumor microenvironment, matrix hardness change and mechanical factors interferences. Then we would further uncover the mechanism of Sorafenib resistance and discover new targets for HCC treatment. This project conforms to the idea of "precision medicine" and has important value from the translational medicine aspect.