舌癌是常见的头颈部肿瘤，严重影响患者的生命安全和生存质量。FAT非典型钙黏素与果蝇中Fat抑癌基因高度同源，然而人类中FAT的四个基因在肿瘤中的功能还存在争议，其表达的调控机制以及作用的分子机制目前还不清楚。本课题组的前期研究发现，FAT1在舌癌中表达升高而FAT4在舌癌中表达下降，而FAT1表达下调后抑制了舌癌细胞的增殖、迁移能力，我们推测在舌癌中FAT1可能是促进因子，FAT4可能是抑制因子，FAT2和FAT3的功能尚不清晰。本课题应用分子生物学技术，首先系统分析舌癌样本中四个FAT基因表达水平与拷贝数变化、DNA甲基化以及基因突变的关系，其次探讨这四个基因对舌癌细胞增殖、迁移、粘附能力的影响以及相应的分子机制，同时分析相应的突变对舌癌细胞生物学行为的影响以及对信号通路活化的影响，最后分析这些基因以及相应的突变对舌癌细胞体内转移能力的影响，为发现新的舌癌治疗靶标提供理论和实验依据。

Tongue cancer is a common head and neck carcinoma and seriously lower the quality of life and threat the survival of patients. The four vertebrate FAT atypical cadherins are orthologous to Drosophila fat tumor suppressor gene, but their function in the carcinogenesis and progression of cancer are still controversial, the underlying mechanisms how these genes are regulated and how these genes regulate the cellular signal pathway are still unknown. Our preliminary data shows that FAT1 was up-regulated and FAT4 was down-regulated in tongue cancer tissues, and knockdown of FAT1 inhibits the proliferation and migration of tongue cancer cells, which indicate that FAT1 plays oncogenic roles and FAT4 may be a tumor suppressor gene in tongue cancer. The goal of the proposed study is to analyze the expression of FAT genes in tongue cancer tissues and its relationship with DNA methylation, loss of heterozygosity, and gene mutation, to explore the roles of FAT genes and their cancer-related mutants in the proliferation, adhesion, migration, and the activation of cellular signal pathway of tongue cancer cells. Finally, we want to investigate the effect of FAT genes and their mutant on metastasis in vivo using high metastatic potential cell line. These studies will provide novel insights into the mechanisms that how FAT genes are dysregulated in tongue cancer and their roles in tumorgenesis and metastasis of tongue cancer, perhaps providing new therapeutic targets to battle this devastating disease.