DACT3 is an epigenetic regulator of Wnt/b-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications (Cancer Cell, 2008, 13:529-541)

報告日期: 2008/11/21
報告時間: 15:10/16:00
報告學生: 蘇珮\誼
講評老師: 賴明德
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971121-1.pdf

DACT3 Is an Epigenetic Regulator of Wnt/β-Catenin Signaling in Colorectal Cancer and Is a Therapeutic Target of Histone Modifications

 

Cancer Cell 13, 529–541, June 2008

 

Speaker蘇珮誼

Commentator賴明德老師

Date:2008.11.21

Room: 602

 

Abstract:

Wnt/β-catenin pathway plays an important role to regulate cell proliferation and survival. Many studies demonstrated that aberrant activation of Wnt/β-catenin signaling lead to cancer. In cancer cell, both genetic mutations in Wnt/β-catenin pathway components and epigenetic regulation can contribute to aberrant activation of this signaling pathway. Members of the DACT(dpr/Frodo) gene family have been shown to modulate Wnt/β-catenin signaling by interacting with Dishevelled (Dvl), a central component Wnt signaling. In this study, authors found DACT3, a member of the DACT (dpr/Frodo) gene family, was transcriptionally repressed and then was identified as a epigenetic regulator of Wnt/β-catenin signaling in colorectal cancer. By employing Illumina Human Ref-8_V2 Sentrix BeadChip and Methylation special PCR (MSP), authors demonstrated that repression of DACT3 was associated with bivalent histone modification in colorectal cancer cell line. A pharmacological combination that simultaneously targets both histone methylation and deacetylation can derepress DACT3 expression and then lead to inhibition of Dishevelled mediated Wnt/β-catenin signaling and massive apoptosis in colorectal cancer cells. Furthermore, cancer cells transfected with DACT3 show a dramatic decrease in colony numbers compared to control cells.

Taken these data together, authors suggest that DACT3 is an epigenetic regulator of Wnt/β-catanin signaling in colorectal cancer and also functions as a potential tumor suppressor as therapeutic control strategy in colorectal cancer.

 

Reference:

1. Cheyette, B.N., Waxman, J.S., Miller, J.R., Takemaru, K., Sheldahl, L.C., Khlebtsova, N., Fox, E.P., Earnest, T., and Moon, R.T. (2002). Dev. Cell 2, 449–461.

2. Zhang, L., Gao, X., Wen, J., Ning, Y., and Chen, Y.G. (2006). J. Biol. Chem, 281, 8607–8612.