ArticleBlood advances2021
DKK1 activates noncanonical NF-κB signaling via IL-6-induced CKAP4 receptor in multiple myeloma.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Factors affecting the role of canonical Wnt inhibitor Dickkopf-1 in cancer progression.Frontiers in oncology · 2023Pooled it
- Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.Cell biochemistry and function · 2026Review
- DKK1 activated the NF-κB pathway by binding with CKAP4 to induce PASMC oxidative stress and promote pulmonary arterial hypertension.Genes & genomics · 2026Article
- DKK1 in Cancer: A Bench-to-Bedside Review of Molecular Mechanisms and Clinical Applications.Cancers · 2026Review
- The Dickkopf-1 (DKK1) Dichotomy in Oncology: New Insights on Tumor Progression and Immune Regulation.International journal of molecular sciences · 2026Review
- The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.Journal of bone oncology · 2025Review
- CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma.Genes & genomics · 2025Article
- Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma.Scientific reports · 2025Article
- AI-driven discovery of minimal sepsis biomarkers for disease detection and progression: precision medicine across diverse populations.Frontiers in medicine · 2025Article
- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
- Protective effects of butorphanol in oleic acid-endotoxin "two-hit" induced rat lung injury by suppression of inflammation and apoptosis.Scientific reports · 2024Article
- Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.Oncogene · 2024Article
- Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.Nature communications · 2024Article
- Article
- The Clinical Relevance of Selected Cytokines in Newly Diagnosed Multiple Myeloma Patients.Biomedicines · 2023Article
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- Macrophages and Urokinase Plasminogen Activator Receptor System in Multiple Myeloma: Case Series and Literature Review.International journal of molecular sciences · 2023Review
- [Latest Findings on the Mechanism of the Interaction Between Multiple Myeloma Cells and Bone Marrow Microenvironment].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
- Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Review
- Advances in the pathogenesis of multiple myeloma bone disease.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciencesArticle
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome inhibitors, such as bortezomib (BTZ), represent the key elements in chemotherapy regimens for multiple myeloma (MM), whereas acquired chemoresistance and ultimately relapse remain a major obstacle. In the current study, we screened differently expressed cytokines in bortezomib-resistant MM cells and found that Dickkopf-1 (DKK1) level was remarkably augmented, whereas CD138 level was significantly suppressed. DKK1 in vitro specifically enhanced the resistance of myeloma cells to bortezomib treatment, and excessive DKK1 drove CD138 downregulation via inhibition of canonical Wnt signaling. Notably, DKK1 mainly induced drug resistance in MM cells via the receptor of CKAP4. Mechanistically, CKAP4 transduced DKK1 signal and evoked NF-κB pathway through recruiting and preventing cullin associated and neddylation dissociated 1 from hampering the assembly of E3 ligase-mediated ubiquitination of IκBα. In addition, we found that interleukin-6 (IL-6) stimulated CKAP4 expression to generate drug resistance, and disturbance of DKK1-CKAP4 axis improved sensitivity to BTZ treatment of MM and attenuated bone destruction in a mouse model. Collectively, our study revealed the previously unidentified role of DKK1 in myeloma drug resistance via Wnt signaling dependent and independent manners, and clarified the importance of antagonism of DKK1-IL-6 loop in bone marrow microenvironment.
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