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

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

Author Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Ribeiro, Helem Ferreira Google Scholar
Antonio Rey, Juan Google Scholar
Pinto, Giovanny Reboucas Google Scholar
Smith, Marilia Cardoso Autor UNIFESP Google Scholar
Moreira-Nunes, Caroline Aquino Google Scholar
Assumpcao, Paulo Pimentel Google Scholar
Lamarao, Leticia Martins Google Scholar
Calcagno, Danielle Queiroz Google Scholar
Montenegro, Raquel Carvalho Google Scholar
Burbano, Rommel Rodriguez Google Scholar
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.
Keywords gastric cancer
cancer development
YWHAE
CDC25B
MYC
xmlui.dri2xhtml.METS-1.0.item-coverage Orchard Park
Language English
Date 2016
Published in Oncotarget. Orchard Park, v. 7, n. 51, p. 85393-85410, 2016.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 85393-85410
Origin http://dx.doi.org/10.18632/oncotarget.13381
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000391353200128
URI https://repositorio.unifesp.br/handle/11600/56542

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