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Cyr61/CCN1 Is Regulated by Wnt/β-Catenin Signaling and Plays an Important Role in the Progression of Hepatocellular Carcinoma.
- Source :
-
PLoS ONE . Apr2012, Vol. 7 Issue 4, p1-9. 9p. - Publication Year :
- 2012
-
Abstract
- Abnormal activation of the canonical Wnt signaling pathway has been implicated in carcinogenesis. Transcription of Wnt target genes is regulated by nuclear β-catenin, whose over-expression is observed in Hepatocellular Carcinoma (HCC) tissue. Cyr61, a member of the CCN complex family of multifunctional proteins, is also found over-expressed in many types of tumor and plays dramatically different roles in tumorigenesis. In this study, we investigated the relationship between Cyr61 and β-catenin in HCC. We found that while Cyr61 protein was not expressed at a detectable level in the liver tissue of healthy individuals, its expression level was elevated in the HCC and HCC adjacent tissues and was markedly increased in cancer-adjacent hepatic cirrhosis tissue. Over-expression of Cyr61 was positively correlated with increased levels of bcatenin in human HCC samples. Activation of β-catenin signaling elevated the mRNA level of Cyr61 in HepG2 cells, while inhibition of β-catenin signaling reduced both mRNA and protein levels of Cyr61. We identified two TCF4-binding elements in the promoter region of human Cyr61 gene and demonstrated that β-catenin/TCF4 complex specifically bound to the Cyr61 promoter in vivo and directly regulated its promoter activity. Furthermore, we found that over-expression of Cyr61 in HepG2 cells promoted the progression of HCC xenografts in SCID mice. These findings indicate that Cyr61 is a direct target of β-catenin signaling in HCC and may play an important role in the progression of HCC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CATENINS
*LIVER cancer
*DISEASE progression
*GENE expression
*CARCINOGENESIS
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 79918170
- Full Text :
- https://doi.org/10.1371/journal.pone.0035754