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

Pygopus-2 promotes invasion and metastasis of hepatic carcinoma cell by decreasing E-cadherin expression.
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Pygopu​​s-2通过降低E-cadherin表达促进肝癌细胞的侵袭和转移。

DOI:
10.18632/oncotarget.3570
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发表时间:
2015-05-10
期刊:
影响因子:
--
通讯作者:
Wang X
Wang X
中科院分区:
其他
文献类型:
--
作者:
Zhang S;Li J;Liu P;Xu J;Zhao W;Xie C;Yin Z;Wang X

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据报道,Pygopus-2在几种恶性肿瘤中过表达,如卵巢癌、乳腺癌、肺癌和肝癌。在这里,我们证明了shRNA下调了Pygopus-2的表达,抑制了肝癌细胞的体外侵袭和移植瘤模型中的转移,而当Pygopus-2过表达时,这种抑制作用被促进了。Pygopus-2通过降低E-钙粘附素而增加肝癌细胞的侵袭和转移。Pygopus-2可与E-钙粘蛋白启动子结合,增加其甲基化,并间接降低ZEB2的表达。反过来,这些效应导致E-钙粘蛋白的下调,增强了侵袭和转移。我们认为靶向Pygopus-2可能抑制肝癌的转移。
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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影响因子: --
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