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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.

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