11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell migration and invasion

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Activation of Snail1 signaling promotes the migration and invasion of multiple tumors, including glioblastoma multiforme (GBM). However, the molecular mechanism that augments Snail1 signaling during GBM cell migration and invasion remains largely unknown. Identification of the factors that regulate Snail1 signaling is critical to block tumor cell migration and invasion. By screening human GBM specimens, we found that the expression levels of small GTPase RND3 positively correlated with the expression levels of E-cadherin and claudin, the glioblastoma migration biomarkers negatively regulated by Snail1. Downregulation of E-cadherin and claudin has been associated with the migration and invasion of GBM cells. We demonstrated that RND3 functioned as an endogenous inhibitor of the Snail-directed transcriptional regulation. RND3 physically interacted with Snail1 protein, enhanced Snail1 ubiquitination, and facilitated the protein degradation. Forced expression of RND3 inhibited Snail1 activity, which in turn blocked glioblastoma cell migration and invasion in vitro in cell culture and in vivo in GBM xenograft mice. In contrast, downregulation of RND3 augmented Snail1 activity, and subsequently decreased E-cadherin expression, eventually promoted glioblastoma cell migration and invasion. The pro-migration induced by RND3 downregulation was attenuated by Snail1 knockdown. The findings partially explain why Snail1 activity is augmented in GBM, and defines a new function of RND3 in GBM cell migration and invasion.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness.

          The Notch signaling pathway maintains a balance between cell proliferation and apoptosis, and thus it is believed that Notch signaling pathways may play an important role in the development and progression of several malignancies. However, the functions of Notch signaling in EMT are largely unknown. This mini review describes the role of Notch signaling pathway in EMT, and cataloging how its deregulation is involved in EMT and tumor aggressiveness. Further attempts have been made to summarize the role of several chemopreventive agents that could be useful for targeted inactivation of Notch signaling, and thus it may cause reversal of EMT, which could become a novel approach for cancer prevention and treatment.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Epithelial-to-mesenchymal(-like) transition as a relevant molecular event in malignant gliomas.

            Tumor dissemination and metastatic behavior account for the vast majority of cancer associated mortality. Epithelial tumors achieve this progressive state via epithelial-to-mesenchymal transition (EMT); however, the importance of this process in the neuroepithelial context is currently very controversially discussed. The review describes the current research status concerning EMT-like changes in malignant gliomas including the role of TWIST1, ZEB1/ZEB2 and SNAIl1/SNAIl2 as inducers for cell-invasiveness in GBMs. Furthermore, WNT/β-catenin signaling with its key-component FRIZZLED4 activating an EMT-like program in malignant gliomas and its relationship to the stem-like phenotype as well as discoveries on micro-RNA-level regulating the EMT-like process are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Transport of molecules, particles, and cells in solid tumors.

              R Jain (1998)
              Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.
                Bookmark

                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                13 December 2016
                1 October 2016
                : 7
                : 50
                : 82411-82423
                Affiliations
                1 Department of Neurological Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
                2 Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA
                3 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
                Author notes
                Correspondence to: Jiang Chang, jchang@ 123456ibt.tamhsc.edu
                Article
                12396
                10.18632/oncotarget.12396
                5347701
                27705942
                9060977b-219c-4a7d-93df-68b90259501b
                Copyright: © 2016 Liu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 May 2016
                : 24 September 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                rnd3,multiform glioblastoma,snail1 signaling
                Oncology & Radiotherapy
                rnd3, multiform glioblastoma, snail1 signaling

                Comments

                Comment on this article