ArticleOncology research2018
DKK3 Overexpression Increases the Malignant Properties of Head and Neck Squamous Cell Carcinoma Cells.
Article in Oncology research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Integrative Mendelian Randomization and Single-Cell Pseudotime Analysis Reveal DKK3 as a PI3K-AKT-Modulated Driver of Esophageal Squamous Cell Carcinoma.Human mutation · 2026Article
- Article
- Review
- The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.Cells · 2023Review
- Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC).Cancer cell international · 2022Article
- LINC00958 may be a new prognostic biomarker in various cancers: A meta-analysis and bioinformatics analysis.Frontiers in genetics · 2022Review
- Article
- TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma.Journal of Cancer · 2021Article
- The Clinical Significance of Dickkopf Wnt Signaling Pathway Inhibitor Gene Family in Head and Neck Squamous Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- MicroRNA-3690 promotes cell proliferation and cell cycle progression by altering DKK3 expression in human thyroid cancer.Oncology letters · 2020Article
- Methylation Assessment of TwoIranian journal of public health · 2020Article
- Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials.International journal of molecular sciences · 2020Review
- miR-1303 promotes the proliferation, migration and invasion of prostate cancer cells through regulating the Wnt/β-catenin pathway by targeting DKK3.Experimental and therapeutic medicine · 2019Article
- Dickkopf Homolog 3Frontiers in oncology · 2019Article
- Knockdown of RWD domain containing 3 inhibits the malignant phenotypes of glioblastoma cells via inhibition of phosphoinositide 3-kinase/protein kinase B signaling.Experimental and therapeutic medicine · 2018Article
- The clinicopathological and prognostic significances of Dkk3 expression in cancers: A bioinformatics analysis.Cancer biomarkers : section A of Disease markers · 2018Article
- Apolipoprotein E Promotes Invasion in Oral Squamous Cell Carcinoma.The American journal of pathology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DKK3, a member of the dickkopf Wnt signaling pathway inhibitor family, is believed to be a tumor suppressor because of its reduced expression in cancer cells. However, our previous studies have revealed that DKK3 expression is predominantly observed in head and neck/oral squamous cell carcinoma (HNSCC/OSCC). Interestingly, HNSCC/OSCC patients with DKK3 expression showed a high rate of metastasis and poorer survival, and siRNA-mediated knockdown of DKK3 in HNSCC-derived cancer cell lines resulted in reduced cellular migration and invasion. From these data, it was hypothesized that DKK3 might exert an oncogenic function specific to HNSCC. In the present research, the DKK3 overexpression model was established, and its influences were investigated, together with molecular mechanism studies. The DKK3 expression profile in cancer cell lines was investigated, including HNSCC/OSCC, esophageal, gastric, colorectal, pancreatic, prostatic, and lung cancers. DKK3 overexpression was performed in HNSCC-derived cells by transfection of expression plasmid. The effects of DKK3 overexpression were assessed on cellular proliferation, migration, invasion, and in vivo tumor growth. The molecular mechanism of DKK3 overexpression was investigated by Western blotting and microarray analysis. DKK3 overexpression significantly elevated cellular proliferation, migration, and invasion, as well as increased mRNA expression of cyclin D1 and c-myc. However, reporter assays did not show TCF/LEF activation, suggesting that the increased malignant property of cancer cells was not driven by the Wnt/β-catenin pathway. For the investigation of the pathways/molecules in DKK3-mediated signals, the Western blot analyses revealed that phosphorylation of Akt (S473) and c-Jun (Ser63) was elevated. The application of a PI3K kinase inhibitor, LY294002, on HSC-3 DKK3 cells significantly decreased tumor cell proliferation, migration, and invasion. From these results, we demonstrated that DKK3 might contribute to cellular proliferation, invasion, migration, and tumor cell survival in HNSCC cells through a mechanism other than the canonical Wnt signaling pathway, which might be attributed to PI3K-Akt signaling.
Indexed as
Identifiers
What 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.