Cui Yuehong, Wang Yan, Li Hong, Li Qian, Yu Yiyi, Xu Xiaojing, Xu Bei, Liu Tianshu
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Oncotarget. 2016 Jun 7;7(23):34356-70. doi: 10.18632/oncotarget.8879.
Asparaginyl endopeptidase (AEP) is a lysosomal protease and overexpressive in gastric cancer. AEP was higher expressive in peritoneal metastatic loci than that in primary gastric cancer. Then we overexpressed AEP or knocked it down with a lentiviral vector in gastric cancer cell lines and detected the cell cycle arrest and the changes of the invasive and metastatic ability in vitro and in vivo. When AEP was knocked-down, the proliferative, invasive and metastatic capacity of gastric cancer cells were inhibited, and the population of sub-G1 cells increased. The expressive level of twist, which is a transcriptional factor, decreased significantly, and the epithelial markers' expression of EMT, E-cadherin increased, but that of the mesenchymal markers, N-cadherin, β-catenin and Vimentin decreased, if AEP was knocked down. These results showed that AEP could promote invasion and metastasis by modulating EMT. We used phosphorylation-specific antibody microarrays to investigate the mechanism that AEP promotes gastric cancer invasion and metastasis, and found that the phosphorylation level of AKT and MAPK signaling pathways were decreased significantly if AEP was knocked-down. Therefore, AKT and MAPK signaling pathways took part in the modulation.
天冬酰胺基内肽酶（AEP）是一种溶酶体蛋白酶，在胃癌中过表达。AEP在腹膜转移灶中的表达高于原发性胃癌。然后我们在胃癌细胞系中通过慢病毒载体过表达或敲低AEP，并检测其在体外和体内的细胞周期阻滞以及侵袭和转移能力的变化。当AEP被敲低时，胃癌细胞的增殖、侵袭和转移能力受到抑制，亚G1期细胞数量增加。如果AEP被敲低，作为转录因子的twist的表达水平显著降低，上皮间质转化（EMT）的上皮标志物E-钙黏蛋白的表达增加，而间质标志物N-钙黏蛋白、β-连环蛋白和波形蛋白的表达降低。这些结果表明，AEP可通过调节EMT促进侵袭和转移。我们使用磷酸化特异性抗体微阵列研究AEP促进胃癌侵袭和转移的机制，发现如果AEP被敲低，AKT和MAPK信号通路的磷酸化水平显著降低。因此，AKT和MAPK信号通路参与了这种调节。
