22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Members of the EpCAM signalling pathway are expressed in gastric cancer tissue and are correlated with patient prognosis

      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

          Background:

          We investigated the expression of members of the epithelial cell adhesion molecule (EpCAM) signalling pathway in gastric cancer (GC) testing the following hypotheses: are these molecules expressed in GC and are they putatively involved in GC biology.

          Methods:

          The study cohort consisted of 482 patients. The following members of the EpCAM signalling pathway were analysed by immunohistochemistry and were correlated with various clinico-pathological patient characteristics: extracellular domain of EpCAM (EpEX), intracellular domain of EpCAM (EpICD), E-cadherin, β-catenin, presenilin-2 (PSEN2), and ADAM17.

          Results:

          All members of the EpCAM signalling pathway were differentially expressed in GC. The expression correlated significantly with tumour type (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), mucin phenotype (EpEX, EpICD, β-catenin, and ADAM17), T-category (EpEX, E-cadherin, and β-catenin), N-category (EpEX and β-catenin), UICC tumour stage (EpEX, EpICD, β-catenin, and PSEN2), tumour grade (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), and patients' survival (EpEX, EpICD, and PSEN2). A significant coincidental expression in GC was found for EpEX, EpICD, E-cadherin, β-catenin, PSEN2, and ADAM17. Decreased immunodetection of EpEX in locally advanced GC was not associated with decreased EpCAM mRNA levels.

          Conclusion:

          All members of the EpCAM signalling pathway are expressed in GC. The expression correlated significantly with each other and with various clinico-pathological patient characteristics, including patients' survival. Thus, the EpCAM signalling pathway is a highly interesting putative therapeutic target in GC.

          Related collections

          Most cited references21

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

          Nuclear signalling by tumour-associated antigen EpCAM.

          EpCAM was found to be overexpressed on epithelial progenitors, carcinomas and cancer-initiating cells. The role of EpCAM in proliferation, and its association with cancer is poorly explained by proposed cell adhesion functions. Here we show that regulated intramembrane proteolysis activates EpCAM as a mitogenic signal transducer in vitro and in vivo. This involves shedding of its ectodomain EpEX and nuclear translocation of its intracellular domain EpICD. Cleavage of EpCAM is sequentially catalysed by TACE and presenilin-2. Pharmacological inhibition or genetic silencing of either protease impairs growth-promoting signalling by EpCAM, which is compensated for by EpICD. Released EpICD associates with FHL2, beta-catenin and Lef-1 to form a nuclear complex that contacts DNA at Lef-1 consensus sites, induces gene transcription and is oncogenic in immunodeficient mice. In patients, EpICD was found in nuclei of colon carcinoma but not of normal tissue. Nuclear signalling of EpCAM explains how EpCAM functions in cell proliferation.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The emerging role of EpCAM in cancer and stem cell signaling.

            Initially discovered as a dominant antigen on colon carcinomas, the epithelial cell adhesion molecule (EpCAM) was considered a mere cell adhesion molecule and reliable surface-binding site for therapeutic antibodies. Recent findings can better explain the relevance of EpCAM's high-level expression on human cancers and cancer propagating cells, and its negative prognostic potential for survival of patients with certain cancers. EpCAM has oncogenic potential and is activated by release of its intracellular domain, which can signal into the cell nucleus by engagement of elements of the wnt pathway.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              EpCAM (CD326) finding its role in cancer

              Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.
                Bookmark

                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                15 October 2013
                05 September 2013
                : 109
                : 8
                : 2217-2227
                Affiliations
                [1 ]Department of Pathology, Christian-Albrechts-University , Arnold-Heller-Strasse, D-24105 Kiel, Germany
                [2 ]Faculty of Clinical Medicine Mannheim, Department of Medicine II, University of Heidelberg , Mannheim, Germany
                Author notes
                Article
                bjc2013536
                10.1038/bjc.2013.536
                3798952
                24008668
                812ac0fa-dcc6-465a-bc94-79c465bc7f42
                Copyright © 2013 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 24 February 2013
                : 04 August 2013
                : 14 August 2013
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                gastric cancer,epcam,berep4,epicd,psen2,adam17
                Oncology & Radiotherapy
                gastric cancer, epcam, berep4, epicd, psen2, adam17

                Comments

                Comment on this article