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


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





Room: 602



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.



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