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YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE role in the tumor development and metastasis process

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      Abstract

      We previously observed reduced YWHAE (14-3-3ε) protein expression in a small set of gastric cancer samples. YWHAE may act as a negative regulator of the cyclin CDC25B, which is a transcriptional target of MYC oncogene. The understanding of YWHAE role and its targets is important for the better knowledge of gastric carcinogenesis. Thus, we aimed to evaluate the relationship among YWHAE, CDC25B, and MYC in vitro and in vivo. For this, we analyzed the YWHAE, CDC25B, and MYC expression in YWHA-silenced, CDC25B-silenced, and MYC-silenced gastric cancer cell lines, as well as in gastric cancer and non-neoplastic gastric samples. In gastric cancer cell lines, YWHAE was able to inhibit the cell proliferation, invasion and migration through the reduction of MYC and CDC25B expression. Conversely, MYC induced the cell proliferation, invasion and migration through the induction of CDC25B and the reduction of YWHAE. Most of the tumors presented reduced YWHAE and increased CDC25B expression, which seems to be important for tumor development. Increased MYC expression was a common finding in gastric cancer and has a role in poor prognosis. In the tumor initiation, the opposite role of YWHAE and CDC25B in gastric carcinogenesis seems to be independent of MYC expression. However, the inversely correlation between YWHAE and MYC expression seems to be important for gastric cancer cells invasion and migration. The interaction between YWHAE and MYC and the activation of the pathways related to this interaction play a role in the metastasis process.

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      Most cited references 62

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            Author and article information

            Affiliations
            1 Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil
            2 Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, Brazil
            3 Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Belém, Brazil
            4 Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil
            5 Laboratorio de Oncogenética Molecular, Hospital Universitario La Paz, Madrid, Spain
            6 Departmento de Biomedicina, Universidade Federal do Piauí, Parnaíba, Brazil
            7 Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil
            8 Laboratório de Testes de Ácidos Nucleicos, Fundação Centro de Hemoterapia e Hematologia do Pará, Belém, Brazil
            9 Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belém, Brazil
            Author notes
            Correspondence to: Mariana Ferreira Leal, mariana.morf@ 123456epm.br
            Journal
            Oncotarget
            Oncotarget
            Oncotarget
            ImpactJ
            Oncotarget
            Impact Journals LLC
            1949-2553
            20 December 2016
            16 November 2016
            : 7
            : 51
            : 85393-85410
            27863420
            5356744
            13381
            10.18632/oncotarget.13381
            Copyright: © 2016 Leal 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.

            Categories
            Research Paper

            Oncology & Radiotherapy

            myc, cdc25b, ywhae, cancer development, gastric cancer

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