ArticleAmerican journal of cancer research2019
Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.
Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Prognostic role of dickkopf-1 in patients with cancer.Medicine · 2020Pooled it
- 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 Emerging Role of CKAP4 in GI Cancer: From Molecular Pathways to Clinical Applications.Current oncology (Toronto, Ont.) · 2025Review
- Knockdown of WISP1/DKK1 restrains phenotypic plasticity in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition and stemness.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.Diagnostics (Basel, Switzerland) · 2025Review
- Identification of a Novel Intracellular Function of the Secreted Ribonuclease RNASE1 in Inhibiting Gene Expression.Molecular and cellular biology · 2025Article
- Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/β-catenin pathways in hepatocellular carcinoma.Cell communication and signaling : CCS · 2023Article
- Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer.Molecular biotechnology · 2023Article
- Research progress on the role of the Wnt signaling pathway in pituitary adenoma.Frontiers in endocrinology · 2023Review
- A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma.Frontiers in oncology · 2022Article
- Article
- Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer.Carcinogenesis · 2021Article
- Article
- The pro-angiogenesis effect of miR33a-5p/Ets-1/DKK1 signaling in ox-LDL induced HUVECs.International journal of biological sciences · 2021Article
- Identification of an Immune-Related Biomarker Model Based on the CircRNA-Associated Regulatory Network for Esophageal Carcinoma.Journal of oncology · 2021Article
- Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway.International journal of biological sciences · 2021Article
- Identification of a four-gene panel predicting overall survival for lung adenocarcinoma.BMC cancer · 2020Article
- Construction and Validation of a 7-Immune Gene Model for Prognostic Assessment of Esophageal Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Oligometastatic Gastroesophageal Adenocarcinoma: Molecular Pathophysiology and Current Therapeutic Approach.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Esophageal adenocarcinoma (EAC) is still associated with poor prognosis, despite modern multi-modal therapies. New molecular markers, which control cell cycle and promote lymph node metastases or tumor growth, may introduce novel target therapies. Dickkopf-1 (DKK1) is a secreted glycoprotein that blocks the oncogenic Wnt/β-catenin signaling and its aberrant expression has been observed in many malignancies, including EAC. In this study, we investigated the biological role of DKK1 in EAC. Analysis of DKK1 and active β-catenin expression in human esophageal tissues confirmed a simultaneous DKK1-overexpression together with aberrant activation of β-catenin signaling in EAC in comparison with Barrett's and healthy mucosa. To elucidate the molecular role of DKK1, the OE33 adenocarcinoma cells, which were found to overexpress DKK1, were subjected to functional and molecular assays following siRNA-mediated DKK1-knockdown. At the functional level, OE33 cell viability, proliferation, migration and invasion were significantly attenuated by the absence of DKK1. At the molecular level, neither DKK1-knockdown nor application of exogenous recombinant DKK1 were found to alter the baseline β-catenin signaling in OE33 cells. However, DKK1-knockdown significantly abrogated downstream Akt-phosphorylation. On the other hand, the Wnt-agonist, Wnt3a, restored the Akt-phorphorylation in the absence of DKK1, without, however, being able to further stimulate β-catenin transcription. These findings suggest that the β-catenin transcriptional activity in EAC is independent of Wnt3a/DKK1 site-of-action and define an oncogenic function for DKK1 in this type of malignancy via distinct activation of Akt-mediated intracellular pathways and independently of Wnt-axis inhibition. Taken together, DKK1 may present a novel therapeutic target in EAC.
Indexed as
Identifiers
30906632PMC6405970W2981056196What OpenQuestion holds
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.