IR@PKUHSC  > 北京大学第三临床医学院  > 普通外科
学科主题临床医学
Oncogenic Function of DACT1 in Colon Cancer through the Regulation of beta-catenin
Yuan, Guohong; Wang, Chongkai; Ma, Chaolai; Chen, Ning; Tian, Qinghe; Zhang, Tonglin; Fu, Wei
刊名PLOS ONE
2012-03-21
DOI10.1371/journal.pone.0034004
7期:3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Science Foundation of China ; National Science Foundation of China
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ADENOMATOUS POLYPOSIS-COLI ; GLYCOGEN-SYNTHASE KINASE-3-BETA ; SIGNALING PATHWAY ; XENOPUS EMBRYOS ; DOWN-REGULATION ; NUCLEAR EXPORT ; WNT SIGNALS ; APC ; CARCINOMA ; CELLS
英文摘要

The Wnt/beta-catenin signaling pathway plays important roles in the progression of colon cancer. DACT1 has been identified as a modulator of Wnt signaling through its interaction with Dishevelled (Dvl), a central mediator of both the canonical and noncanonical Wnt pathways. However, the functions of DACT1 in the WNT/beta-catenin signaling pathway remain unclear. Here, we present evidence that DACT1 is an important positive regulator in colon cancer through regulating the stability and sublocation of beta-catenin. We have shown that DACT1 promotes cancer cell proliferation in vitro and tumor growth in vivo and enhances the migratory and invasive potential of colon cancer cells. Furthermore, the higher expression of DACT1 not only increases the nuclear and cytoplasmic fractions of beta-catenin, but also increases its membrane-associated fraction. The overexpression of DACT1 leads to the increased accumulation of nonphosphorylated beta-catenin in the cytoplasm and particularly in the nuclei. We have demonstrated that DACT1 interacts with GSK-3 beta and beta-catenin. DACT1 stabilizes beta-catenin via DACT1-induced effects on GSK-3 beta and directly interacts with beta-catenin proteins. The level of phosphorylated GSK-3 beta at Ser9 is significantly increased following the elevated expression of DACT1. DACT1 mediates the subcellular localization of beta-catenin via increasing the level of phosphorylated GSK-3 beta at Ser9 to inhibit the activity of GSK-3 beta. Taken together, our study identifies DACT1 as an important positive regulator in colon cancer and suggests a potential strategy for the therapeutic control of the beta-catenin-dependent pathway.

语种英语
所属项目编号30770440
资助者National Science Foundation of China ; National Science Foundation of China
WOS记录号WOS:000303857100064
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52429
Collection北京大学第三临床医学院_普通外科
作者单位Peking Univ, Dept Gen Surg, Hosp 3, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Yuan, Guohong,Wang, Chongkai,Ma, Chaolai,et al. Oncogenic Function of DACT1 in Colon Cancer through the Regulation of beta-catenin[J]. PLOS ONE,2012,7(3).
APA Yuan, Guohong.,Wang, Chongkai.,Ma, Chaolai.,Chen, Ning.,Tian, Qinghe.,...&Fu, Wei.(2012).Oncogenic Function of DACT1 in Colon Cancer through the Regulation of beta-catenin.PLOS ONE,7(3).
MLA Yuan, Guohong,et al."Oncogenic Function of DACT1 in Colon Cancer through the Regulation of beta-catenin".PLOS ONE 7.3(2012).
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