IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling
Yu, Yuanzi1,2; Yan, Wenji1; Liu, Xuefeng1; Jia, Yan1,3; Cao, Baoping1,4; Yu, Yingyan5; Lv, Youyong6; Brock, Malcolm V.7; Herman, Jame G.7; Licchesi, Julien7; Yang, Yunsheng1; Guo, Mingzhou1
关键词Gastric cancer DACT2 DNA methylation Wnt signaling pathway chemo-sensitivity
刊名AMERICAN JOURNAL OF CANCER RESEARCH
2014
4期:6页:710-724
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]BETA-CATENIN ; HEPATOCELLULAR-CARCINOMA ; PATHWAY ; GENE ; INHIBITOR ; DAPPER2 ; CARCINOGENESIS ; EXPRESSION ; ZEBRAFISH ; 6Q27
英文摘要

Dapper, Dishevelled-associated antagonist of beta-catenin (DACT), is a key regulator of Wnt signaling pathway. The purpose of this study is to explore the epigenetic changes and the function of DACT2 in human gastric cancer (GC). Eight human gastric cancer cell lines, 167 cases of primary gastric cancer and 8 cases of normal gastric mucosa were involved in this study. In addition, methylation Specific PCR (MSP), semi-quantitative RT-PCR, colony formation assay, flow cytometry assay, siRNA, immunofluorescence techniques and xenograft mice models were employed. The results indicate that DACT2 is frequently methylated in human primary gastric cancer (55.7%), and that methylation of DACT2 is associated with lost or reduction in its expression (X-2 test, P<0.01). We found that DACT2 expression was regulated by promoter region hypermethylation. Methylation of DACT2 is associated with tumor differentiation, invasion and intravascular cancerous emboli (X-2 test, P<0.05, P<0.05 and P<0.05). In gastric cancer patients treated with 5-FU and cisplatin, the five-year survival rates are higher in DACT2 methylated cases. DACT2 inhibits cell proliferation, migration and invasion in gastric cancer cells and suppresses gastric cancer xenografts in mice. Restoration of DACT2 expression inhibits both canonical and noncanonical WNT signaling in SGC7901 cells. Restoration of DACT2 expression sensitized gastric cancer cells to paclitaxel and 5-FU. In conclusion, DACT2 is frequently methylated in human gastric cancer and DACT2 expression is silenced by promoter region hypermethylation. DACT2 suppressed gastric cancer proliferation, invasion and metastasis by inhibiting Wnt signaling both in vitro and in vivo.

语种英语
WOS记录号WOS:000346855300009
项目编号2012CB934002 ; 2010CB912802 ; SS2012AA020314 ; SS2012AA020821 ; SS2012AA020303 ; 2011YQ03013405 ; 81121004 ; 81071953 ; 81161120432
资助机构National Basic Research Program (973 Program) ; National High-tech R&amp ; D Program (863 Program) ; National Key Scientific instrument Special Programme of China ; National Science Foundation of China
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62685
专题北京大学临床肿瘤学院
作者单位1.Tianjin Med Univ Canc Inst & Hosp, Tianjin 300060, Peoples R China
2.Nankai Univ, Coll Med, Tianjin 300071, Peoples R China
3.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing 100853, Peoples R China
4.Shandong Univ, Prov Hosp, Dept Gastroenterol, Jinan 250021, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200240, Peoples R China
6.Peking Univ, Sch Oncol, Beijing Inst Canc Res, Beijing 100034, Peoples R China
7.Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
推荐引用方式
GB/T 7714
Yu, Yuanzi,Yan, Wenji,Liu, Xuefeng,et al. DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2014,4(6):710-724.
APA Yu, Yuanzi.,Yan, Wenji.,Liu, Xuefeng.,Jia, Yan.,Cao, Baoping.,...&Guo, Mingzhou.(2014).DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling.AMERICAN JOURNAL OF CANCER RESEARCH,4(6),710-724.
MLA Yu, Yuanzi,et al."DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling".AMERICAN JOURNAL OF CANCER RESEARCH 4.6(2014):710-724.
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