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学科主题: 临床医学
题名:
DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling
作者: 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
发表日期: 2014
卷: 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
所属项目编号: 2012CB934002 ; 2010CB912802 ; SS2012AA020314 ; SS2012AA020821 ; SS2012AA020303 ; 2011YQ03013405 ; 81121004 ; 81071953 ; 81161120432
项目资助者: 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
WOS记录号: WOS:000346855300009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62685
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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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

Recommended Citation:
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.
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