Open AccessWip1 suppresses ovarian cancer metastasis through the ATM/AKT/Snail mediated signaling
Author(s) -
Sheng Yin,
Pan Wang,
Lina Yang,
Yang Liu,
Yan Wang,
Mingming Liu,
Qi Zhou,
Jiao Meng,
Ting Shi,
Gong Yang,
Rongyu Zang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8833
Subject(s) - protein kinase b , metastasis , cancer research , gene silencing , snail , ovarian cancer , small hairpin rna , cancer , pi3k/akt/mtor pathway , gene knockdown , biology , medicine , phosphorylation , signal transduction , cell culture , microbiology and biotechnology , ecology , biochemistry , genetics , gene
Inactivation of p53 greatly contributes to serous ovarian cancer, while the role of the wild-type p53 induced phosphatase 1 (Wip1) is quite unclear. In this study, by silencing or overexpression of Wip1, we found that Wip1 suppressed ovarian cancer cell invasion, migration, epithelial to mesenchymal transition (EMT), and ovarian cancer metastasis in xenograft animal models. Mechanistic studies showed that Wip1 may block ovarian cancer metastasis through inhibition of Snail and p-Akt expression because silencing or overexpression of Wip1 either upregulated or downregulated the expression of Snail and p-Akt (Ser 473), while further knockdown of Snail by shRNA or inhibition of p-Akt by a chemical compound attenuated cell invasion, migration and EMT in Wip1 silencing cells. We also found that the phosphorylation of Akt at Ser 473 might be mediated through p-ATM (Ser 1981). Thus, Wip1 may suppress ovarian cancer metastasis through negative regulation of p-ATM, p-Akt, and Snail, which was also evidenced in the limited clinical specimens. Therefore, our data may provide a novel therapeutic indication for serous ovarian cancer based on the uncovered mechanism associated with the precise function of Wip1 independent of p53.