ArticleClinical epigenetics2018
The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via β-catenin/Cdc25c signaling and G2/M arrest.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 45 citations in OpenAlex.
- COLEC12 promotes pancreatic cancer progression via the activation of the TGF-β signaling pathway.Molecular and cellular biochemistry · 2026Article
- A new signature associated with anoikis predicts the outcome and immune infiltration in nasopharyngeal carcinoma.Discover oncology · 2025Article
- Tumor immune microenvironment of colorectal cancer identifies novel prognostic signature and potential therapeutic drugs.Cancer biomarkers : section A of Disease markers · 2024Article
- Integrated transcriptomics of human blood vessels defines a spatially controlled niche for early mesenchymal progenitor cells.Developmental cell · 2024Article
- PDCD2 as a prognostic biomarker in glioma correlates with malignant phenotype.Genes & diseases · 2024Article
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- Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- MeCP2 confers 5-fluorouracil resistance in gastric cancer via upregulating the NOX4/PKM2 pathway.Cancer cell international · 2022Article
- ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis.Cellular and molecular life sciences : CMLS · 2022Article
- ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance.International journal of biological sciences · 2022Article
- The Role of DACT Family Members in Tumorigenesis and Tumor Progression.International journal of biological sciences · 2022Review
- Mapk14 is a Prognostic Biomarker and Correlates with the Clinicopathological Features and Immune Infiltration of Colorectal Cancer.Frontiers in cell and developmental biology · 2022Article
- DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application.Clinical epigenetics · 2021Review
- Targeting the signaling in Epstein-Barr virus-associated diseases: mechanism, regulation, and clinical study.Signal transduction and targeted therapy · 2021Review
- When Viruses Cross Developmental Pathways.Frontiers in cell and developmental biology · 2021Review
- Identification of a DNA Methylation-Driven Genes-Based Prognostic Model and Drug Targets in Breast Cancer:Frontiers in immunology · 2021Article
- Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis.Clinical epigenetics · 2020Article
- Study on the chemodrug-induced effect in nasopharyngeal carcinoma cells using laser tweezer Raman spectroscopy.Biomedical optics express · 2020Article
- Effect of Ect2 Expression on the Growth of Triple-Negative Breast Cancer Cells with Paclitaxel Intervention.OncoTargets and therapy · 2020Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNasopharyngeal carcinoma (NPC) is prevalent in South China, including Hong Kong and Southeast Asia, constantly associated with Epstein-Barr virus (EBV) infection. Epigenetic etiology attributed to EBV plays a critical role in NPC pathogenesis. Through previous CpG methylome study, we identified Disheveled-associated binding antagonist of beta-catenin 2 (DACT2) as a methylated target in NPC. Although DACT2 was shown to regulate Wnt signaling in some carcinomas, its functions in NPC pathogenesis remain unclear.
methodsRT-PCR, qPCR, MSP, and BGS were applied to measure expression levels and promoter methylation of DACT2 in NPC. Transwell, flow cytometric analysis, colony formation, and BrdU-ELISA assay were used to assess different biological functions affected by DACT2. Immunofluorescence, Western blot, and dual-luciferase reporter assay were used to explore the mechanisms of DACT2 functions. Chemosensitivity assay was used to measure the impact of DACT2 on chemotherapy drugs.
resultsWe found that DACT2 is readily expressed in multiple normal adult tissues including upper respiratory tissues. However, it is frequently downregulated in NPC and correlated with promoter methylation. DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored its expression in NPC cells. DACT2 methylation was further detected in 29/32 (91%) NPC tumors but not in any (0/8) normal nasopharyngeal tissue samples. Ectopic expression of DACT2 in NPC cells suppressed their proliferation, migration, and invasion through downregulating matrix metalloproteinases. DACT2 expression also induced G2/M arrest in NPC cells through directly suppressing β-catenin/Cdc25c signaling, which sensitized NPC cells to paclitaxel and 5-FU, but not cisplatin.
conclusionOur results demonstrate that DACT2 is frequently inactivated epigenetically by CpG methylation in NPC, while it inhibits NPC cell proliferation and metastasis via suppressing β-catenin/Cdc25c signaling. Our study suggests that DACT2 promoter methylation is a potential epigenetic biomarker for the detection and chemotherapy guidance of NPC.
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