共 53 条
DACT3 is an epigenetic regulator of Wnt/β-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications
被引:209
作者:

Jiang, Xia
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机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Tan, Jing
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Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Li, Jingsong
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h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Kivimaee, Saul
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Grad Programs Dev Biol & Neurosci, Dept Psychiat, San Francisco, CA 94158 USA Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Yang, Xiaojing
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h-index: 0
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Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Zhuang, Li
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h-index: 0
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Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Lee, Puay Leng
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h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Chan, Mark T. W.
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h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Stanton, Lawrence W.
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h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Stem Cell & Dev Biol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Liu, Edison T.
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h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Cheyette, Benjamin N. R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Grad Programs Dev Biol & Neurosci, Dept Psychiat, San Francisco, CA 94158 USA Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore

Yu, Qiang
论文数: 0 引用数: 0
h-index: 0
机构:
Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore
机构:
[1] Biopolis, ASTAR, Genome Inst Singapore, Canc Biol & Pharmacol, Singapore 138672, Singapore
[2] Univ Calif San Francisco, Grad Programs Dev Biol & Neurosci, Dept Psychiat, San Francisco, CA 94158 USA
[3] Biopolis, ASTAR, Genome Inst Singapore, Stem Cell & Dev Biol, Singapore 138672, Singapore
来源:
关键词:
D O I:
10.1016/j.ccr.2008.04.019
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Genetic and epigenetic defects in Wnt/beta-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/beta-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly derepressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/beta-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/beta-catenin signaling in colorectal cancer and suggests a potential strategy for therapeutic control of Wnt/beta-catenin signaling in colorectal cancer.
引用
收藏
页码:529 / 541
页数:13
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