The expression of presenilin 1 enhances carcinogenesis and metastasis in gastric cancer
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Ping Li1, Xi Lin1, Jun-Rong Zhang1, Yun Li2, Jun Lu1, Fei-Chao Huang1, Chao-Hui Zheng1, Jian-Wei Xie1, Jia-Bin Wang1, Chang-Ming Huang1
1Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
2Key Laboratory of the Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
Chang-Ming Huang, e-mail: email@example.com
Ping Li, e-mail: firstname.lastname@example.org
Keywords: PS-1, gastric cancer, tumorigenicity, E-cadherin, β-catenin
Received: August 21, 2015 Accepted: January 19, 2016 Published: February 10, 2016
Presenilin 1 (PS-1, encoded by PSEN1) is a part of the gamma− (γ−) secretase complex. Mutations in PSEN1 cause the majority of cases of familial Alzheimer’s disease (FAD). Although in recent years PS-1 has been implicated as a tumor enhancer in various cancers, nothing is known regarding its role in gastric cancer (GC). In the present study, we investigate the role and clinical significance of PS-1 in GC. We observed that PS-1 was significantly upregulated and amplified in GC tissues and cell lines, and its aberrant expression was positively correlated with lymph node metastasis and with poor overall survival. Furthermore, PS-1 promoted tumor invasion and metastasis of GC both in vitro and vivo without affecting the proliferation of GC cells (MGC-803 and MKN-45). The results of treatment with the γ-secretase inhibitor DAPT were consistent with the outcomes of PS-1 silencing. PS-1/γ-secretase cleaves E-cadherin and releases its bound protein partner, β-catenin, from the actin cytoskeleton, thereby allowing it to translocate into the nucleus and to activate the TCF/LEF-1 transcriptional activator, which may promote GC invasion and metastasis.
In conclusion, PS-1 promotes invasion and metastasis in GC and may represent a novel prognostic biomarker and potential therapeutic target for GC treatment.
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