远处转移仍是导致胰腺癌患者死亡的主要原因。肿瘤定植是转移灶形成的重要环节，但相关研究报道不多。单细胞极性是影响远处定植的重要因素，而Ezrin是诱导单细胞极性的关键分子，但其调控机制尚不清楚。本课题组前期证实dysbindin可直接结合PI3K，提高下游AKT通路活性；最近研究发现dysbindin可诱导胰腺癌单细胞极化，促进Ezrin磷酸化。因此，我们推测dysbindin可能通过PI3K-AKT-Ezrin信号轴，调控胰腺癌单细胞极性，促进肿瘤远处定植。本课题拟在前期基础上，进一步检测胰腺癌中dysbindin表达与单细胞极性的相关性；利用细胞、动物模型验证dysbindin对单细胞极性和定植能力的影响；结合蛋白组学方法探讨dysbindin调控单细胞极性的分子机制。本研究将揭示dysbindin在调控单细胞极性、促进胰腺癌转移定植中的作用和地位，为抑制胰腺癌转移提供新的潜在分子靶点。

Metastasis is the main cause of death for pancreatic cancer. Tumor colonization is an important segment of metastasis, while few studies have been reported. Single cell polarity is a vital factor for metastatic colonization, and Ezrin is the key molecule. Our group previously had demonstrated that dysbindin can bind with PI3K directly and enhance its kinase activity. Recent study revealed that dysbindin induced single cell polarization of pancreatic cancer cells and induced the phosphorylation of Ezrin. Therefore, it was speculated that dysbindin may regulate the single cell polarity of pancreatic cancer and promote metastatic colonization through the PI3K-AKT-Ezrin signaling axis. In this study, we attempt to detect the correlation between dysbindin expression and single-cell polarity in pancreatic cancer, verify the effect of dysbindin on the single cell polarity in pancreatic cancer cells, as well as the metastatic colonization in animal models, on the basis of previous research. We will also investigate the molecular mechanism of dysbindin in modulating single cell polarity using proteomic approaches. This study will explore the role of dysbindin in regulating single-cell polarity and metastatic colonization of pancreatic cancer, thus providing a new potential molecular target for inhibiting pancreatic cancer metastasis.