Abstract
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.
Keywords:
E-cadherin; hepatic carcinoma; invasion; metastasis; pygopus-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Blotting, Western
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Cadherins / genetics*
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Cadherins / metabolism
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / secondary*
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Cell Movement*
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Cell Proliferation
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Chromatin Immunoprecipitation
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DNA Methylation
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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Immunoenzyme Techniques
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology*
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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Promoter Regions, Genetic / genetics
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Cadherins
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Intracellular Signaling Peptides and Proteins
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PYGO2 protein, human
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RNA, Messenger
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RNA, Small Interfering