FAT1调控YAP1信号通路抑制宫颈癌EMT发生的作用及机制研究

宫颈癌是最常见的妇科肿瘤之一，传统治疗后复发率仍高，我们前期对部分预后差、转移复发患者的宫颈癌组织样本进行免疫组化染色后发现上皮标志物表达降低，间质标志物表达升高。与此同时，针对宫颈癌患者的基因组测序发现了FAT1的突变，随后我们利用生物信息学手段对突变位点进行了功能预测，发现这些突变几乎均对蛋白质功能产生较为严重的损害。本课题为前期工作的继续和深入。首先通过临床样本研究FAT1突变和表达与宫颈癌浸润转移及预后的关系。再拟以宫颈癌细胞系为研究对象，在体外应用免疫共沉淀、激光共聚焦显微镜、分子生物学相关技术研究FAT1对YAP1的调控机制以及FAT1通过YAP1对宫颈癌细胞EMT转变的影响及机制。并通过裸鼠移植瘤模型在体内进一步证实FAT1通过YAP1调控宫颈癌细胞的EMT转变。旨在为探索FAT1在子宫颈癌的发生发展中的作用，以及为其突变相关的宫颈癌靶向治疗提供理论支持和实验依据。

Cervical cancer is one of the most common gynecological tumor, recurrence rate after conventional treatment is still high. The invasion and metastasis of cervical cancer is closely related to the epithelial-mesenchymal transition (EMT). We performed Immunohistochemical staining and found decreased expression of epithelial marker and increased expression of mesenchymal marker in cervical cancer tissues with poor prognosis and metastasis. At the same time, mutations in the FAT1 was found for the first time in cervical cancer by genome sequencing. Then we used biological informatics tools to predict these mutations are almost causing significantly deleterious effect on protein function. Based on our previous work, this study is trying to explore the regulation function and mechanism of FAT1 on YAP1 and the effect of FAT1 on epithelial-mesenchymal transition of cervical cancer cell through YAP1 in vitro using co-IP, laser scanning confocal microscopy, molecular biological techniques and so on, and the EMT of cervical cancer cell regulated by FAT1 through YAP1 in vivo using transplanted tumor model. Mean while, the relationship between mutated FAT1 and invasion/metastasis of cervical cancer will be studied. Its aim is to provide theoretical support and experimental basis of target therapy Aimed at the FAT1 mutation in cervical cancer. All above is to provide theoretical support and experimental basis of target therapy of cervical cancer with FAT1 mutation.