复发转移是乳腺癌病人最终死亡的主要原因。研究发现外周髓鞘蛋白-22(PMP22)在侵袭性乳腺癌细胞中高表达，并且与预后相关，但其机制尚不清楚。我们前期实验发现PMP22能够促进乳腺癌细胞转移，诱导AKT与Pygo2蛋白磷酸化修饰。我们还新发现Pygo2蛋白PHD结构域具有AKT的底物序列，能够被AKT磷酸化修饰，从而增强与Bcl9的结合能力，进而增强Wnt信号通路。值得注意的是PMP22是Wnt信号通路靶基因，提示PMP22与Wnt存在正反馈回路。本项目在前期工作基础上，拟采用分子细胞生物学方法结合实验动物模型，研究PMP22在乳腺癌发生中的生物学功能，研究PMP22促进上皮-间质转化(EMT)过程中的潜在作用与调控机制，并扩大临床样本容量，明确PMP22在乳腺癌肿瘤转移过程中的病理学意义，验证PMP22作为乳腺癌循环肿瘤细胞标志物应用于临床检测的可能性，为后续转化医学研究奠定基础。

Recurrence and metastasis are the main causes of death in breast cancer patients and yet the underlying mechanism remains to be solved. It's found that peripheral myelin protein-22 (PMP22) is highly expressed in metastatic breast cancer and may serve as prognostic factor for patient outcome, with mechanism unknown. Our preliminary data showed that over-expression of PMP22 could promote migration of breast cancer cells, potentially through phosphorylation of AKT and Pygo2. Further, Pygo2 PHD domain contains AKT recognition site and could be phosphorylated by AKT, which modification could enhance Pygo2’s interaction with Bcl9, and thus augment Wnt signaling. More interestingly, PMP22 is a down stream target of Wnt signaling pathway, indicating a positive feedback mechanism. Based on our preliminary discovery, this project aims to uncover PMP22's biological function in breast cancer tumor genesis and its potential role and mechanism in Epithelial to mesenchymal transition (EMT), by using molecular and cellular approaches as well as mouse model. Additionally, we will expand our studies of clinical samples in order to verify the function of PMP22 in breast cancer metastasis and to explore its potential as clinical marker for identifying circulating breast cancer cells. All of these will pave ways for the following translational biomedical research.