DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling.

作者：Yuanzi Yu, Wenji Yan, Xuefeng Liu, Yan Jia, Baoping Cao, Yingyan Yu, Youyong Lv, Malcolm V. Brock, J Herman, Julien Licchesi, Yunsheng Yang, Mingzhou Guo · 发表于：Pure (University of Bath) · 年份：2014 · 被引用次数：42 · 研究领域：Cancer-related gene regulation、Epigenetics and DNA Methylation、Wnt/β-catenin signaling in development and cancer

Dapper, Dishevelled-associated antagonist of β-catenin (DACT), is a key regulator of Wnt signaling pathway. The purpose of this study is to explore the epigenetic changes and the function ofDACT2 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 huma...