Journal
ONCOTARGET
Volume 7, Issue 9, Pages 10650-10662Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7298
Keywords
PS-1; gastric cancer; tumorigenicity; E-cadherin; beta-catenin
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Funding
- National Key Clinical Specialty Discipline Construction Program of China [[2012]649]
- Young and Middle-aged Talent Training Project of the Fujian Provincial Health and Family Planning Commission [2014-ZQN-JC-13]
- Youth Research Projects of the Fujian Provincial Health and Family Planning Commission [2015-1-37]
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Presenilin 1 (PS-1, encoded by PSEN1) is a part of the gamma-(gamma-) 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.-secretase inhibitor DAPT were consistent with the outcomes of PS-1 silencing. PS-1/gamma-secretase cleaves E-cadherin and releases its bound protein partner, beta-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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