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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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      Abstract

      Background

      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.

      Purpose

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

      Methods

      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.

      Results

      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.

      Conclusion

      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.

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      Most cited references 32

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            Author and article information

            Affiliations
            Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China, trwujixiang2017@ 123456126.com
            Author notes
            Correspondence: Jixiang Wu, Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, No 2 Chongwenmennei Street, Dongcheng, Beijing 100730, China, Tel +86 1 380 101 5118, Email trwujixiang2017@ 123456126.com
            Journal
            Onco Targets Ther
            Onco Targets Ther
            OncoTargets and Therapy
            OncoTargets and therapy
            Dove Medical Press
            1178-6930
            2018
            19 July 2018
            : 11
            : 4177-4187
            6056154 10.2147/OTT.S172713 ott-11-4177
            © 2018 Ge et al. This work is published and licensed by Dove Medical Press Limited

            The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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            Original Research

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