Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Guo,Li; Wang,Xiaohong; Yang,Yuguang; Xu,Hongchun; Zhang,Zhihong; Yin,Lili; Wang,Yan; Yang,Maopeng; Zhao,Shu; Bai,Shuping; Zhao,Ling; Wang,Zhipeng; Lian,Xin; Liu,Ying; Zhang,Qingyuan

doi:10.3892/ol.2017.7633

Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Authors:
- Li Guo
- Xiaohong Wang
- Yuguang Yang
- Hongchun Xu
- Zhihong Zhang
- Lili Yin
- Yan Wang
- Maopeng Yang
- Shu Zhao
- Shuping Bai
- Ling Zhao
- Zhipeng Wang
- Xin Lian
- Ying Liu
- Qingyuan Zhang
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Affiliations: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Department of Thoracic Surgery, Mudanjiang Tumor Hospital, Mudanjiang, Heilongjiang 157000, P.R. China, Obstetrics and Gynecology Department, General Hospital of Daqing Oil Field, Daqing, Heilongjiang 163000, P.R. China, Obstetrics and Gynecology Department, Heilongjiang Electric Power Hospital, Harbin, Heilongjiang 150090, P.R. China, Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/ol.2017.7633
Pages: 3287-3294

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Abstract

The activation of the Wnt/β‑catenin signaling pathway has been demonstrated to play important roles in breast carcinogenesis and to be associated with a poorer prognosis in breast cancer patients. However, genetic mutation is not the major reason for Wnt/β‑catenin activation in breast cancer. Dishevelled‑associated antagonist of β‑catenin homolog 2 (DACT2) is a negative regulator of β‑catenin and acts as a tumor suppressor in numerous cancer types; however, the expression change and potential role of DACT2 in breast cancer is unknown. The present study detected the expression and function of DACT2 in breast cancer progression. It was identified that the expression of DACT2 significantly decreased in breast cancer tissues compared with paired adjacent normal breast tissues. Additional investigation demonstrated that the hypermethylation of DACT2 gene promoter contributes to the loss of the gene in breast cancer. It was also demonstrated that DACT2 is a tumor suppressor in breast cancer and inhibits the proliferation and invasion of breast cancer cells by repressing the expression of β‑catenin target genes associated with tumor growth and metastasis. The present study indicates that the loss of DACT2 may contribute to breast cancer progression and provides a promising therapeutic target for the treatment of breast cancer.

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