ArticleOncotarget2017
Dickkopf-related protein 2 induces G0/G1 arrest and apoptosis through suppressing Wnt/β-catenin signaling and is frequently methylated in breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Genome-Wide Association Study for Milk Protein Content in Romanian Dual-Purpose Cattle.Life (Basel, Switzerland) · 2025Article
- ADCY4 inhibits cAMP-induced growth of breast cancer by inactivating FAK/AKT and ERK signaling but is frequently silenced by DNA methylation.Scientific reports · 2025Article
- Cancer Stem Cell Regulation as a Target of Therapeutic Intervention: Insights into Breast, Cervical and Lung Cancer.Cell biochemistry and biophysics · 2025Review
- The assessment of Dickkopf-1 and Dickkopf-2 protein concentration in different subtypes of non-small cell lung cancer subtypes.Contemporary oncology (Poznan, Poland) · 2024Article
- Advances in understanding the role and mechanisms of tumor stem cells in HER2-positive breast cancer treatment resistance (Review).International journal of oncology · 2023Review
- Microglial Expression of the Wnt Signaling ModulatoreNeuro · 2023Article
- Retinoic acid effects on in vitro palatal fusion and WNT signaling.European journal of oral sciences · 2022Article
- Promoter methylation analysis ofAsian biomedicine : research, reviews and news · 2022Article
- Wnt Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Transcriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma.American journal of translational research · 2021Article
- Wnt ligands 3a and 5a regulate proliferation and migration in human fetal liver progenitor cells.Translational gastroenterology and hepatology · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling.Clinical epigenetics · 2020Article
- Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma.Cancers · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- 19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer.Theranostics · 2020Article
- New Insights into the Implication of Epigenetic Alterations in the EMT of Triple Negative Breast Cancer.Cancers · 2019Review
- TUFT1 Promotes Triple Negative Breast Cancer Metastasis, Stemness, and Chemoresistance by Up-Regulating the Rac1/β-Catenin Pathway.Frontiers in oncology · 2019Article
- Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer.Theranostics · 2019Article
- Regional Control of Hairless versus Hair-Bearing Skin by Dkk2.Cell reports · 2018Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dickkopf-related protein 2 (DKK2) is one of the antagonists of Wnt/β-catenin signaling, with its downregulation reported in multiple cancers. However, how DKK2 contributes to breast tumorigenesis remains unclear. We examined its expression and promoter methylation in 10 breast tumor cell lines, 98 primary tumors, and 21 normal breast tissues. Compared with normal tissues, DKK2 was frequently silenced in breast cell lines (7/8). DKK2 promoter methylation was detected in 77.8% of cell lines and 86.7% of breast tumors; while rarely detected in normal breast tissues (19%), indicating common DKK2 methylation in breast cancer. Ectopic expression of DKK2 changed breast tumor cell morphology, inhibited cell proliferation and colony formation by inducing G0/G1 cell cycle arrest and apoptosis, and suppressed tumor cell migration by reversing epithelial-mesenchymal transition (EMT) and downregulating stem cell markers. Moreover, restored expression of DKK2 in MCF7 cells disrupted the microtube formation of human umbilical vein endothelial cells on Matrigel®. In vivo, the growth of MDA-MB-231 cells in nude mice was markedly decreased after stable expression of DKK2. DKK2 suppressed canonical Wnt/β-catenin signaling by inhibiting β-catenin activity with decreased active β-catenin protein. Thus, our findings demonstrate that DKK2 functions as a tumor suppressor through inhibiting cell proliferation and inducing apoptosis via regulating Wnt signaling during breast tumorigenesis.
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