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Methylation of DACT2 promotes breast cancer development by activating Wnt signaling.

ABSTRACT: Breast cancer is the most common malignant tumor in women worldwide. To explore the role of DACT2 in breast cancer, 5 cell lines and 153 cases of primary cancer were studied. The expression of DACT2 was detected in BT474, MDA-MB-231 and BT549 cells, while no expression was found in MDA-MB-468 and HBL100 cells. Complete methylation of DACT2 was found in MDA-MB-468 and HBL100 cells, partial methylation was observed in BT474 and BT549 cells, and no methylation was detected in MDA-MB-231 cells. Restoration of DACT2 expression was induced by 5-Aza in MDA-MB-468 and HBL100 cells. DACT2 was methylated in 49.7% (76/153) of primary breast cancer samples. Methylation of DACT2 was significantly associated with tumor size (P?

SUBMITTER: Li J

PROVIDER: S-EPMC5468316 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Methylation of DACT2 promotes breast cancer development by activating Wnt signaling.

Li Jingyi J Zhang Meiying M He Tao T Li Hongxia H Cao Tingting T Zheng Lili L Guo Mingzhou M

Scientific reports 20170612 1

Breast cancer is the most common malignant tumor in women worldwide. To explore the role of DACT2 in breast cancer, 5 cell lines and 153 cases of primary cancer were studied. The expression of DACT2 was detected in BT474, MDA-MB-231 and BT549 cells, while no expression was found in MDA-MB-468 and HBL100 cells. Complete methylation of DACT2 was found in MDA-MB-468 and HBL100 cells, partial methylation was observed in BT474 and BT549 cells, and no methylation was detected in MDA-MB-231 cells. Rest ...[more]

PMID: 28607412

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Project description:Thyroid cancer is the most common endocrine malignant disease and the incidence is increasing. DACT2 was found frequently methylated in human lung cancer and hepatocellular carcinoma. To explore the epigenetic change and the role of DACT2 in thyroid cancer, 7 thyroid cancer cell lines, 10 cases of non-cancerous thyroid tissue samples and 99 cases of primary thyroid cancer samples were involved in this study. DACT2 was expressed and unmethylated in K1, SW579, FTC-133, TT, W3 and 8505C cell lines. Loss of expression and complete methylation was found in TPC-1 cells. Restoration of DACT2 expression was induced by 5-aza-2'deoxycytidine treatment. It demonstrates that the expression of DACT2 was regulated by promoter region methylation. In human primary papillary thyroid cancer, 64.6% (64/99) was methylated and methylation of DACT2 was related to lymph node metastasis (p<0.01). Re-expression of DACT2 suppresses cell proliferation, invasion and migration in TPC-1 cells. The activity of TCF/LEF was inhibited by DACT2 in wild-type or mutant β-catenin cells. The activity of TCF/LEF was increased by co-transfecting DACT2 and Dvl2 in wild-type or mutant β-catenin cells. Overexpression of wild-type β-catenin promotes cell migration and invasion in DACT2 stably expressed cells. The expression of β-catenin, c-myc, cyclinD1 and MMP-9 were decreased and the level of phosphorylated β-catenin (p-β-catenin) was increased after restoration of DACT2 expression in TPC-1 cells. The expression of β-catenin, c-myc, cyclinD1 and MMP-9 were increased and the level of p-β-catenin was reduced after knockdown of DACT2 in W3 and SW579 cells. These results suggest that DACT2 suppresses human papillary thyroid cancer growth and metastasis by inhibiting Wnt signaling. In conclusion, DACT2 is frequently methylated in papillary thyroid cancer. DACT2 expression was regulated by promoter region methylation. DACT2 suppresses papillary thyroid cancer proliferation and metastasis by inhibiting Wnt signaling.

Project description:Purpose:Evidence describing TMED3 in the context of breast cancer is scarce, and the effect of TMED3 on Wnt/?-catenin signaling in breast cancer has not been reported. The objective of this study was to determine the potential physiological functions and molecular mechanisms of TMED3 in breast cancer. Materials and Methods:Quantitative real-time PCR and Western blot analysis were used to analyze the expression of TMED3 mRNA and protein in 182 paraffin-embedded primary breast cancer tissues and 60 paired noncancerous tissues and 25 fresh primary breast cancer tissues and surrounding adjacent noncancerous tissues. Associations between TMED3 expression and clinicopathologic factors or overall survival were determined. The effects of overexpression or knockdown of TMED3 on proliferation, migration, invasion, and cell cycle progression in breast cancer cell lines were investigated with the Cell Counting Kit-8, clone formation assay, transwell assay, wound healing assay, and flow cytometry, respectively. Immunofluorescence and Western blot analysis were used to detect the expression of cell cycle, migration-related, and Wnt/?-catenin signaling proteins. Results:The expression of TMED3 mRNA and protein were significantly increased in breast cancer tissues and cell lines compared to normal controls. TMED3 upregulation was significantly correlated with clinicopathologic characteristics and predicted poor prognosis in patients with breast cancer. TMED3 overexpression promoted proliferation, migration, invasion, and cell cycle progression compared to controls in breast cancer cell lines. TMED3 knockdown suppressed proliferation, migration, invasion, and cell cycle progression compared to controls in breast cancer cell lines. TMED3 promoted proliferation and migration of breast cancer cells by a mechanism that involved Wnt/?-catenin signaling. Conclusion:TMED3 behaves as an oncogene that promotes the proliferation and migration of breast cancer cells by a mechanism that involved Wnt/?-catenin signaling. Strategies targeting TMED3 have potential therapeutic implications for patients with breast cancer.

Dataset Information

Methylation of DACT2 promotes breast cancer development by activating Wnt signaling.

Publications

Methylation of DACT2 promotes breast cancer development by activating Wnt signaling.

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