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Onco Targets Ther. 2018 Jul 19;11:4177-4187. doi: 10.2147/OTT.S172713. eCollection 2018.

DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3β/β-catenin signaling pathway.

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Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China,



Decoy receptor 3 (DcR3) has been reported to be overexpressed in a wide variety of malignancies and is correlated with tumorigenesis and progression. In gastric cancer (GC), DcR3 overexpression is associated with lymph node and distant metastasis, as well as poor prognosis. However, the functional role of DcR3 expression in GC remains elusive.


The aim of this study is to elucidate the direct role of DcR3 in regulating GC progression and metastasis and identify the potential mechanism.


DcR3 expression was stably knocked down in HGC27 and MKN28 cells by transfecting the cells with DcR3 shRNA using lentiviral vector system. After the knockdown of DcR3 was confirmed, cell proliferation, colony formation, cell cycle distribution, apoptosis, cell invasion and migration were assessed in vitro. In addition, Western blot analysis was performed to evaluate the expression of downstream mediators of DcR3. Comparisons between multiple groups were performed using one-way analysis of variance (ANOVA) or unpaired Student's t-test. Differences were considered significant at P<0.05.


Our findings demonstrate that DcR3 induces proliferation, migration, invasion, and promotes epithelial-mesenchymal transition (EMT) of GC cells. In addition, DcR3 increases the expression levels of several components of the PI3K/AKT/GSK-3β/β-catenin signaling pathway, such as p-AKT, GSK-3β, p-GSK-3β and β-catenin. Additionally, DcR3 also enhances the expression of N-cadherin and Vimentin and decreases the expression of E-cadherin.


In summary, the findings of this study indicate that during GC progression, DcR3 plays a key role in cell proliferation and invasion via the PI3K/AKT/GSK-3β/β-catenin signaling pathway. Thus, targeting DcR3 might be a potential therapeutic approach for the treatment of GC.


DcR3; epithelial-mesenchymal transition; gastric cancer; metastasis

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