Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition and analysis of their phosphorylation signaling pathways.
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.
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Yuehong
Y
Cui
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Yan
Y
Wang
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Hong
H
Li
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Qian
Q
Li
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Yiyi
Y
Yu
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaojing
X
Xu
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Bei
B
Xu
Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Tianshu
T
Liu
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099240:Asparaginyl Endopeptidase
D015820:Cadherins; D003546:Cysteine Endopeptidases; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin; D000099240:Asparaginyl Endopeptidase; C495270:CTNNB1 protein, human; C103173:TWIST1 protein, human
asparaginyl endopeptidase; epithelial-to-mesenchymal transition; gastric cancer; metastasis; signaling pathway