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

// Mariana Ferreira Leal 1, 2, 3, * , Helem Ferreira Ribeiro 4, * , Juan Antonio Rey 5 , Giovanny Reboucas Pinto 6 , Marilia Cardoso Smith 1 , Caroline Aquino Moreira-Nunes 7 , Paulo Pimentel Assumpcao 3 , Leticia Martins Lamarao 8 , Danielle Queiroz Calcagno 3 , Raquel Carvalho Montenegro 4 , Rommel Rodriguez Burbano 3, 4, 9 1 Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil 2 Departamento de Ortopedia e Traumatologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil 3 Nucleo de Pesquisas em Oncologia, Hospital Universitario Joao de Barros Barreto, Belem, Brazil 4 Instituto de Ciencias Biologicas, Universidade Federal do Para, Belem, Brazil 5 Laboratorio de Oncogenetica Molecular, Hospital Universitario La Paz, Madrid, Spain 6 Departmento de Biomedicina, Universidade Federal do Piaui, Parnaiba, Brazil 7 Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, Brazil 8 Laboratorio de Testes de Acidos Nucleicos, Fundacao Centro de Hemoterapia e Hematologia do Para, Belem, Brazil 9 Laboratorio de Biologia Molecular, Hospital Ophir Loyola, Belem, Brazil * These authors have contributed equally to this work Correspondence to: Mariana Ferreira Leal, email: mariana.morf@epm.br Keywords: gastric cancer, cancer development, YWHAE, CDC25B, MYC Received: July 10, 2016      Accepted: October 27, 2016      Published: November 16, 2016 ABSTRACT We previously observed reduced YWHAE (14-3-3e) 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.