Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition
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Yuehong Cui1, Yan Wang1,*, Hong Li1, Qian Li1, Yiyi Yu1, Xiaojing Xu1, Bei Xu1, Tianshu Liu1
1Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China
*These authors have contributed equally to this work
Tianshu Liu, email: [email protected]
Keywords: asparaginyl endopeptidase, metastasis, epithelial-to-mesenchymal transition, signaling pathway, gastric cancer
Received: December 11, 2015 Accepted: March 28, 2016 Published: April 20, 2016
Asparaginyl endopeptidase (AEP) is a lysosomal protease often overexpressed in gastric cancer. AEP was expressed higher in peritoneal metastatic loci than 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. AEP knockdown led to significant decrease of expression of transcription factor Twist and the mesenchymal markers N-cadherin, ß-catenin and Vimentin and to increased expression of epithelial marker E-cadherin. These results showed that AEP could promote invasion and metastasis by modulating EMT. We used phosphorylation-specific antibody microarrays to investigate the mechanism how AEP promotes gastric cancer invasion and metastasis, and found that the phosphorylation level of AKT and MAPK signaling pathways was decreased significantly if AEP was knocked-down. Therefore, AKT and MAPK signaling pathways took part in the modulation.
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