title: The expression of presenilin 1 enhances carcinogenesis and metastasis in gastric cancer.
abstract: 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.
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of The Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Fei-Chao
authors.initials: FC
authors.lastname: Huang
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Chao-Hui
authors.initials: CH
authors.lastname: Zheng
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Xie
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Huang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003959:Diamines / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D053764:Presenilin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051820:TCF Transcription Factors / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C000612000:24-diamino-5-phenylthiazole; D015820:Cadherins; D003959:Diamines; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C508853:PSEN1 protein, human; D053764:Presenilin-1; D051820:TCF Transcription Factors; D013844:Thiazoles; D051176:beta Catenin
keywords: E-cadherin; PS-1; gastric cancer; tumorigenicity; β-catenin