明星抑癌基因p53在抑制癌症发生发展过程中起着重要的作用。临床上大约有一半的肿瘤携带有突变型p53。研究表明突变型p53缺失了其原有的抑癌作用，且突变型p53往往表现出促癌特征，尤其是促进肿瘤的增殖及转移。因此，以突变型p53作为癌症的治疗靶点具有重要的意义。本项目依托于中国科学院昆明植物研究所构建的小分子化合物库，计划筛选出特异性的靶向突变型p53肿瘤细胞的增殖转移能力的天然小分子化合物，并进一步确定小分子化合物对携带有突变型p53的肿瘤细胞的作用靶点。通过利用小分子天然化合物库、蛋白质相互作用、蛋白追踪定位、活细胞成像、裸鼠转移瘤模型等体内体外模型，结合多种研究手段，明确小分子化合物抑制携带有突变型p53的肿瘤细胞增殖、侵袭、转移的作用靶点，进一步揭示突变型p53促进肿瘤细胞侵袭转移的新作用机制。本研究结果将为抗肿瘤新药开发提供临床前研究的理论基础和研究方向。

As the guardian of the genome, p53 plays important role in suppressing tumor initiation and progression. Around 50% of malignant tumors habor p53 mutation. Mutant p53 not only lose the tumor suppression ability of wildtype p53, but also gain novel oncogenic functions, such as promoting proliferation, migration, invasion ability of tumor cells, which is defined as mutant p53 gain-of-functions (GOFs). Thus, targeting mutant p53 become a very promising therapeutic strategy towards cancers, which is under intensive investigation. Here, we aim at screening through the natural compounds’ library from Kunming Botany Institute, Chinese Academia of Sciences to find active compounds that specifically targeting mutant p53, especially the cell proliferation ability as well as migration and invasion ability. And the molecular mechanisms of action of active compounds will be further investigated by using biological techniques and chemical biology strategy including the protein-protein interaction, protein tracing, live cell imaging, xenograft tumor models. This project will help identify active compounds that could target mutant p53 GOFs and shed light on explore the novel mechanisms of mutant p53 GOFs.