Pygopus-2 promotes invasion and metastasis of hepatic carcinoma cell by decreasing E-cadherin expression
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Sheng Zhang1,*, Jie Li1,*, Pingguo Liu1, Jianfeng Xu1, Wenxiu Zhao1, Chengrong Xie1, Zhenyu Yin1 and Xiaomin Wang1
1 Department of Hepatobiliary Surgery, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma (Xiamen University Affiliated ZhongShan Hospital), Xiamen, Fujian China
* These authors contributed equally to this work
Xiaomin Wang, email:
Zhenyu Yin, email:
Keywords: pygopus-2, E-cadherin, hepatic carcinoma, invasion, metastasis
Received: January 26, 2015 Accepted: February 22, 2015 Published: March 14, 2015
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 over-expressed. 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.
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