癌症是影响人类健康的主要疾病之一，统计显示约90%的癌症患者死于肿瘤迁移而非原发瘤生长。肿瘤迁移发生的机制尚不清楚，但目前大部分研究都是体外细胞实验，并不能完全反映体内真实情况，因此，利用体内模型进行研究就显得尤为重要。黑腹果蝇具有基因冗余性小和遗传操作简便等优点，已成为研究癌症的主要模式生物。我们利用果蝇体内模型，发现经典Wnt/Wg通路在下调scrib引起的细胞迁移及lgl-/-/RasV12引起的肿瘤浸润中都是充分且必需的。下调经典Wg信号还能抑制JNK引起的细胞迁移，提示其对细胞迁移及肿瘤浸润的调控可能是JNK介导的。本项目拟在此基础上，深入研究经典Wg信号在细胞迁移和肿瘤浸润中的作用，阐明其分子机制，并在癌症病人样本及人类癌细胞中验证。此外，我们也将探究非经典Wg信号在细胞迁移和肿瘤浸润中的作用。这些研究将进一步完善肿瘤迁移的调控网络，为癌症的治疗和药物靶点研究提供新的思路。

Cancer is one of the most fatal diseases that threaten human health. According to statistical analysis, about 90% mortality of cancer patients are caused by tumor metastasis, rather than the growth of primary tumors. However, the molecular mechanism underling tumor metastasis remains elusive. Most of the current research focus on in vitro cancer cells, which can’t fully mimic in vivo tumor metastasis. Thus, it would contribute significantly to cancer treatment if the regulatory mechanisms of tumor metastasis could be investigated using in vivo models. With reduced genome redundancy and many available genetic tools, Drosophila melanogaster has been used as an excellent model organism to study cancers. Using Drosophila in vivo models, we found that the canonical Wg signaling is both necessary and sufficient for loss of scrib induced cell migration and lgl-/-/RasV12 induced tumor invasion. What’s more, our preliminary data indicated that loss of canonical Wg signaling suppresses JNK induced cell migration, indicating a possible mechanism of canonical Wg signaling in regulating cell migration and tumor invasion. Based on these previous results, we will further characterize the role and molecular mechanism of canonical Wg signaling, and validate their orthologs in human cancer cell lines. Meanwhile, we will investigate the possible roles of noncanonical Wg pathways in regulating cell migration and tumor invasion. Thus, this study will not only enrich the signaling network in modulating tumor metastasis, but also provide possible drug targets and therapeutic strategies for clinical cancer treatment.