食管鳞癌转移是其预后差的主要原因，迄今其作用机制尚未清楚阐明。近期研究报道，肿瘤微环境成纤维细胞分泌的Wnt2蛋白促进食管鳞癌EMT和转移。我们前期研究发现，清热解毒类中药灯笼草的新型抗肿瘤活性成分苦蘵内酯P显著抑制Wnt2诱导的食管鳞癌EMT和迁移侵袭，其作用可能与其阻断STAT3活化有关。本研究通过多种食管鳞癌细胞系、斑马鱼转移模型和裸鼠淋巴结转移模型验证苦蘵内酯P抗ESCC迁移侵袭的作用效应。通过慢病毒RNAi、过表达、免疫共沉淀等技术，进一步明确苦蘵内酯P抑制食管鳞癌细胞的STAT3活性，阻断Wnt2蛋白诱导的Fzd2-Fyn-STAT3非经典WNT信号通路活化，进而阻断食管鳞癌细胞EMT和转移侵袭。本研究揭示灯笼草抗肿瘤活性成分苦蘵内酯P抗食管鳞癌转移的作用靶点和分子机制，不仅为灯笼草及其有效成分拓展临床应用提供实验依据，而且为清热解毒类中药防治食管鳞癌转移提供新思路。

Tumor metastasis is the major cause of poor prognosis of esophageal squamous cancer (ESCC), which mechanism has not be elucidated so far. Recently，tumor-fibroblast-secreted Wnt2 can enhance ESCC metastasis by inducing epithelial-mesenchymal transition (EMT). Traditional Chinese Herb Physalis angulata has the function of clearing heat-toxicity. Our previous study found that physagulin P, an active ingredient of Physalis angulata significantly repress EMT by targeting STAT3 activation, resulting in suppressing ESCC cell migration and invasion. In this proposal, we aim to clarify the mechanism and verify therapeutic efficacy of physagulin P by using different ESCC cell lines, zebrafish xenograft and nude mice xenograft . RNAi , overexpression and immunoprecipitation will be applied to prove that physagulin P could interrupt the activation of Wnt2- Fzd2 -Fyn-STAT3 signaling by inhibiting STAT3 activation. This study will not only provide the scientific evidence for clinical application of Physalis angulata and its active ingredients, but also provide a new insight into overcoming ESCC metastasis by using Tranditional Chinese Herb.