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IR@PKUHSC  > 北京大学临床肿瘤学院  > 细胞生物学研究室  > 期刊论文
学科主题: 临床医学
题名:
Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-beta signalling
作者: Yan, Wenji1; Wu, Kongming2; Herman, James G.3; Brock, Malcolm V.3; Zhou, Yusen4; Lu, Youyong5; Zhang, Zhiqian5; Yang, Yunsheng1; Guo, Mingzhou1
关键词: DACH1 ; DNA methylation ; gastric cancer ; invasion ; metastasis ; chemosensitive marker ; docetaxel
刊名: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
发表日期: 2014-12-01
DOI: 10.1111/jcmm.12325
卷: 18, 期:12, 页:2499-2511
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]: Cell Biology ; Research & Experimental Medicine
关键词[WOS]: EPITHELIAL-MESENCHYMAL TRANSITIONS ; FATE DETERMINATION FACTOR ; MATRIX METALLOPROTEINASES ; HEPATOCELLULAR-CARCINOMA ; EXTRACELLULAR-MATRIX ; TISSUE INHIBITORS ; DOWN-REGULATION ; BREAST-CANCER ; TUMOR-GROWTH ; CYCLIN D1
英文摘要:

Gastric cancer (GC) is the fourth most common malignancy in males and the fifth most common malignancy in females worldwide. DACH1 is frequently methylated in hepatic and colorectal cancer. To further understand the regulation and mechanism of DACH1 in GC, eight GC cell lines, eight cases of normal gastric mucosa, 98 cases of primary GC and 50 cases of adjacent non-tumour tissues were examined. Methylation-specific PCR, western blot, transwell assay and xenograft mice were used in this study. Loss of DACH1 expression correlated with promoter region methylation in GC cells, and re-expression was induced by 5-Aza-2-deoxyazacytidine. DACH1 is methylated in 63.3% (62/98) of primary GC and 38% (19/50) of adjacent non-tumour tissues, while no methylation was found in normal gastric mucosa. Methylation of DACH1 correlated with reduced expression of DACH1 (P<0.01), late tumour stage (stage III/IV) (P<0.01) and lymph node metastasis (P<0.05). DACH1 expression inhibited epithelial-mesenchymal transition and metastasis by inhibiting transforming growth factor (TGF)- signalling and suppressed GC cell proliferation through inducing G2/M phase arrest. The tumour size is smaller in DACH1-expressed BGC823 cell xenograft mice than in unexpressed group (P<0.01). Restoration of DACH1 expression also sensitized GC cells to docetaxel. These studies suggest that DACH1 is frequently methylated in human GC and expression of DACH1 was controlled by promoter region methylation. DACH1 suppresses GC proliferation, invasion and metastasis by inhibiting TGF- signalling pathways both in vitro and in vivo. Epigenetic silencing DACH1 may induce GC cells′ resistance to docetaxel.

语种: 英语
所属项目编号: 2012CB934002 ; 2010CB912802 ; SS2012AA020314 ; SS2012AA020821 ; SS2012AA020303 ; 2011YQ03013405 ; 81121004 ; 81071953 ; 81161120432 ; 81072169 ; 81172422 ; 81261120395
项目资助者: National Basic Research Program of China (973 Program) ; National High-tech R&amp ; D Program of China (863 Program) ; National Key Scientific Instrument Special Programme of China ; National Science Foundation of China
WOS记录号: WOS:000345513400018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50825
Appears in Collections:北京大学临床肿瘤学院_细胞生物学研究室_期刊论文

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作者单位: 1.Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21205 USA
2.Chinese Peoples Liberat Army Gen Hosp, Inst Digest Dis, Beijing, Peoples R China
3.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China
4.Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China
5.Peking Univ Sch Oncol, Beijing Inst Canc Res, Dept Cell Biol, Beijing, Peoples R China

Recommended Citation:
Yan, Wenji,Wu, Kongming,Herman, James G.,et al. Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-beta signalling[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2014,18(12):2499-2511.
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