Research Papers:

DACT2 silencing by promoter CpG methylation disrupts its regulation of epithelial-to-mesenchymal transition and cytoskeleton reorganization in breast cancer cells

Tingxiu Xiang, Yichao Fan, Chunhong Li, Lili Li, Ying Ying, Junhao Mu, Weiyan Peng, Yixiao Feng, Michael Oberst, Kathleen Kelly, Guosheng Ren and Qian Tao _

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Oncotarget. 2016; 7:70924-70935. https://doi.org/10.18632/oncotarget.12341

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Tingxiu Xiang1, Yichao Fan2, Chunhong Li3, Lili Li2, Ying Ying2, Junhao Mu1, Weiyan Peng1, Yixiao Feng1, Michael Oberst4, Kathleen Kelly4, Guosheng Ren1, Qian Tao1,2

1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

2Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Hong Kong

3Oncology Department, Suining Sichuan Center Hospital, Sichuan, China

4Signal Transduction Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to:

Guosheng Ren, email: [email protected]

Qian Tao, email: [email protected]

Keywords: DACT2, tumor suppressor, methylation, EMT, breast cancer

Received: April 22, 2016     Accepted: September 14, 2016     Published: September 29, 2016


Wnt signaling plays an important role in breast carcinogenesis. DAPPER2 (DACT2) functions as an inhibitor of canonical Wnt signaling and plays distinct roles in different cell contexts, with its role in breast tumorigenesis unclear. We investigated DACT2 expression in breast cancer cell lines and primary tumors, as well as its functions and molecular mechanisms. Results showed that DACT2 expression was silenced in 9/9 of cell lines. Promoter CpG methylation of DACT2 was detected in 89% (8/9) of cell lines, as well as in 73% (107/147) of primary tumors, but only in 20% (1/5) of surgical margin tissues and in none of normal breast tissues. Demethylation of BT549 and T47D cell lines with 5-aza-2’-deoxycytidine restored DACT2 expression along with promoter demethylation, suggesting that its downregulation in breast cancer is dependent on promoter methylation. Furthermore, ectopic expression of DACT2 induced breast cell apoptosis in vitro, and further inhibited breast tumor cell proliferation, migration and EMT, through antagonizing Wnt/β-catenin and Akt/GSK-3 signaling. Thus, these results demonstrate that DACT2 functions as a tumor suppressor for breast cancer but was frequently disrupted epigenetically in this cancer.

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