Fyn磷酸化修饰调控CD44选择性剪接分子机制的研究

极高的远处转移能力是胰腺癌致死的主要原因，我们既往研究表明，Integrin信号分子Fyn的磷酸化可能是触发这一过程的关键，但详尽机制尚不清楚，结合我们新近的研究发现：胰腺癌细胞在启动胞内Fyn的磷酸化修饰同时，还通过调节瘤细胞CD44v的选择性剪接而影响肿瘤的侵袭转移。本项目拟首先从组织和细胞学水平阐明胰腺癌细胞Fyn的磷酸化修饰机制，再利用可调控的基因表达、免疫共沉淀、siRNA等技术，研究Fyn的磷酸化修饰调控CD44选择性剪接致胰腺癌侵袭转移的分子机制，并进行体内、体外实验验证，最终阐明Fyn磷酸化修饰通过调控CD44选择性剪接而促进胰腺癌转移的分子机制，为临床预测肿瘤转移以及探索诊治新策略提供理论依据。

The metastasis is the main reason of the death of the pancreatic cancer. our previously study showed that, the Fyn, a Non-receptor tyrosine kinases and an integrin signaling molecule, has participated in the metastatic process of pancreatic cancer.our prilimary data showed that the phosphorylated status of Fyn affected the alternative splicing of the CD44 in the pancreatic cancer cells,thus resulted the metastasis of the pancreatic cancer. In this proposal, we initially investigate the mechanism of the Fyn phosphorylation in the cells and tissues, and then apply gene expession , co-immunoprecipatation, RNAi to identify the remodeling expression mechanism of CD44 regulated by Fyn phosporylation.From this study we can make new theories to elucidate metastasis of pancreatic cancer and find a new strategy for the treatments of pancreatic cancer.