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.
Highlights
Hepatic carcinoma (HCC) is the sixth common neoplasm in the world [1]
The above results implied that Pygo2 protein abnormal expression might be associated with HCC cell invasion and metastasis
We used Real-time PCR to detect the mRNA expression pattern and found the similar results that Pygo2 mRNA level was negative associated with E-cadherin (P = 0.0025, r = −0.518, Fig. 3B). These results suggested that E-cadherin was negatively regulated by Pygo2 exist in HCC cell lines, and occur in clinical samples
Summary
Hepatic carcinoma (HCC) is the sixth common neoplasm in the world [1]. The clinical efficacy remains un-satisfactory, despite long-range researches on HCC therapy and the great advance achieved in diagnosis. Recurrence and metastasis are still the main reason for many patients died within three year after the clinical therapy [2] and the 5-year survival rate is no more than 30% [3]. It is of great importance to search effective prediction and valuable markers to precisely protect HCC patients away from recurrence and metastasis. What’s more, our previous study has found that Pygo mRNA and protein expression was significantly higher in HCC tissues, abnormal high expression of Pygo protein in HCC patients correlated with a poor prognosis [17].Obviously, Pygo maybe play an important role in HCC development and progression. Little is known about Pygo functions in HCC cell invasion and metastasis
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