Pygopus-2 promotes invasion and metastasis of hepatic carcinoma cell by decreasing E-cadherin expression

被引:22
作者
Zhang, Sheng [1 ]
Li, Jie [1 ]
Liu, Pingguo [1 ]
Xu, Jianfeng [1 ]
Zhao, Wenxiu [1 ]
Xie, Chengrong [1 ]
Yin, Zhenyu [1 ]
Wang, Xiaomin [1 ]
机构
[1] Xiamen Univ, ZhongShan Hosp, Fujian Prov Key Lab Chron Liver Dis & Hepatocellu, Dept Hepatobiliary Surg, Xiamen, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
pygopus-2; E-cadherin; hepatic carcinoma; invasion; metastasis; STEM-CELLS; WNT; CANCER; CATENIN; PATHWAY; TARGET; MICE; ZEB;
D O I
10.18632/oncotarget.3570
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pygopus-2 over-expression has been reported in several malignancies, such as ovarian, breast, lung and liver cancers. Here we demonstrated that down-regulation of Pygopus-2 by shRNA inhibited hepatic carcinoma cell invasion in vitro and metastasis in xenograft tumor models, which were promoted when Pygopus-2 was overexpressed. Pygopus-2 increased hepatic carcinoma cell invasion and metastasis, by decreasing E-cadherin. Pygopus-2 could bind to the E-cadherin promoter, increasing its methylation, and also indirectly decreased zeb2 expression. In turn these effects caused down-regulation of E-cadherin, potentiating invasion and metastasis. We suggest that targeting Pygopus-2 may potentially inhibit metastasis of hepatic carcinoma.
引用
收藏
页码:11074 / 11086
页数:13
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