肿瘤细胞膜表面蛋白（粘附分子等）在胃癌的转移过程中发挥了重要作用。我们前期研究发现原钙黏蛋白全长PCDH9和PCDH9胞外段在胃癌转移过程中表达下调，而胞内段出现在细胞核内，提示转移过程中PCDH9发生了剪切和核转位，然而其具体机制尚不明确。生物学分析和初步研究显示PCDH9是蛋白水解酶ADAMs的作用底物。ADAMs成员在胃癌中表达升高,能够水解PCDH家族成员,但其对PCDH9的剪切调控促进胃癌转移的研究未见报道。进一步研究发现ADAMs成员受到FoxM1的调控，故我们推测“FoxM1调节ADAMs的表达，调控PCDH9的剪切，促进胃癌细胞的转移”。本课题拟通过基因沉默、过表达、ADAMs抑制剂、质谱等技术研究ADAMs对PCDH9剪切作用，通过突变、免疫共沉淀和ChiP等技术研究FoxM1对ADAMs的调节作用，初步阐明“FoxM1-ADAMs-PCDH9”轴在胃癌转移中的作用。

Cleavaging of molecular on the surface of tumor cells contributes to metastasis of various tumors. Our previous studies revealed that full-length and extracellular domain of PCDH9 decreased with the process of metastasis of gastric cancer and intracellular domain of PCDH9 increased in the nucleus , indicating PCDH9 cleavage and nuclear translocation occurs during metastasis.However, the mechanism underlying this phenomenon remains unclear. Biological analysis showed that the constructure of PCDH9 was easily attacked by ADAMs(a disintegrin and metalloproteases) metalloproteases. ADAMs were upregulated in gastric cancer and resulted in shedding of the extracellular domain of PCDH family. We postulated that ADAMs(ADAM10/17) might be responsible for the downregulation of PCDH9. Interestingly, we found that a novel transcription factor, FoxM1, could regulate the expression of ADAMs(ADAM10/17). Therefore, we postulate that FoxM1 regulates ADAMs expression, which then results in shedding of the extracellular domain of PCDH9. Then metastasis initiated. In the present study, we sought to investigate the role of “FoxM1-ADAMs-PCDH9” axis in the development and progression of human gastric cancer, which will be essential in improving the efficiency of the treatment of gastric cancer and predicting the outcome of patients with gastric cancer.