ArticlePloS one2012
Transcriptional silencing of the Wnt-antagonist DKK1 by promoter methylation is associated with enhanced Wnt signaling in advanced multiple myeloma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.Human molecular genetics · 2014Pooled it
- SUV39H1 regulates progression of pediatric diffuse high-grade gliomas through modulation of β-catenin/TCF4 levels.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Aberrant DNA Methylation Profile of Dickkopf-1 in Ankylosing Spondylitis.Biochemical genetics · 2024Article
- Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq.Genome biology · 2024Article
- The role of Wnt/β-catenin signaling pathway in the pathogenesis and treatment of multiple myeloma (review).American journal of translational research · 2021Review
- Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update.Nature reviews. Clinical oncology · 2020Review
- Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options.Leukemia · 2019Review
- A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.Journal of lipid research · 2019Article
- EBV miR-BART10-3p Promotes Cell Proliferation and Migration by Targeting DKK1.International journal of biological sciences · 2019Article
- WNT Signaling in Cancer Immunosurveillance.Trends in cell biology · 2019Review
- DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.Translational oncology · 2018Article
- Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.Cancers · 2018Review
- Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.Journal of hematology & oncology · 2018Review
- Loss of CYLD expression unleashes Wnt signaling in multiple myeloma and is associated with aggressive disease.Oncogene · 2017Article
- Aberrantly expressed LGR4 empowers Wnt signaling in multiple myeloma by hijacking osteoblast-derived R-spondins.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Identification of candidate genes for myeloma-induced osteocyte death based on microarray data.Journal of orthopaedic surgery and research · 2016Article
- Wnt Signaling in Cancer Stem Cell Biology.Cancers · 2016Review
- Expression and prognostic value of SFRP1 and β-catenin in patients with glioblastoma.Oncology letters · 2016Article
- The putative promoters of germ cell-specific genes and Nanog are hypomethylated in chicken sperm.The Journal of reproduction and development · 2014Article
- Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms.Oncotarget · 2013Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.