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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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      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.

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      Most cited references 32

      • Record: found
      • Abstract: found
      • Article: found

      Global cancer statistics.

      The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
        • Record: found
        • Abstract: found
        • Article: not found

        Wnt/beta-catenin signaling: components, mechanisms, and diseases.

        Signaling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator beta-catenin controls embryonic development and adult homeostasis. Here we review recent progress in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists, and antagonists, and their interactions with Wnt receptors. We also dissect critical events that regulate beta-catenin stability, from Wnt receptors to the cytoplasmic beta-catenin destruction complex, and nuclear machinery that mediates beta-catenin-dependent transcription. Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications.
          • Record: found
          • Abstract: found
          • Article: found

          A perspective on cancer cell metastasis.

          Metastasis causes most cancer deaths, yet this process remains one of the most enigmatic aspects of the disease. Building on new mechanistic insights emerging from recent research, we offer our perspective on the metastatic process and reflect on possible paths of future exploration. We suggest that metastasis can be portrayed as a two-phase process: The first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cell to develop into a metastatic lesion at that distant site. Although much remains to be learned about the second phase, we feel that an understanding of the first phase is now within sight, due in part to a better understanding of how cancer cell behavior can be modified by a cell-biological program called the epithelial-to-mesenchymal transition.

            Author and article information

            Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China, trwujixiang2017@
            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@
            Onco Targets Ther
            Onco Targets Ther
            OncoTargets and Therapy
            OncoTargets and therapy
            Dove Medical Press
            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 and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( 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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