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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Mariana Ferreira Leal1,2,3,*, Helem Ferreira Ribeiro4,*, Juan Antonio Rey5, Giovanny Rebouças Pinto6, Marília Cardoso Smith1, Caroline Aquino Moreira-Nunes7, Paulo Pimentel Assumpção3, Leticia Martins Lamarão8, Danielle Queiroz Calcagno3, Raquel Carvalho Montenegro4, Rommel Rodriguez Burbano3,4,9
1Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil
2Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, Brazil
3Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Belém, Brazil
4Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil
5Laboratorio de Oncogenética Molecular, Hospital Universitario La Paz, Madrid, Spain
6Departmento de Biomedicina, Universidade Federal do Piauí, Parnaíba, Brazil
7Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil
8Laboratório de Testes de Ácidos Nucleicos, Fundação Centro de Hemoterapia e Hematologia do Pará, Belém, Brazil
9Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belém, Brazil
*These authors have contributed equally to this work
Mariana Ferreira Leal, email: [email protected]
Keywords: gastric cancer, cancer development, YWHAE, CDC25B, MYC
Received: July 10, 2016 Accepted: October 27, 2016 Published: November 16, 2016
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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