Evidence map›Paper›PMID 34117362›Full record

ArticleOncogene2021

The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers.

Hirokazu Kimura, Ryota Sada, Naoki Takada, Akikazu Harada, Yuichiro Doki, Hidetoshi Eguchi, Hideki Yamamoto, Akira Kikuchi

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  8. Review
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  10. 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 · 2025
    Article
  11. Article
  12. Review
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  20. FOXM1 promotes TGF-β2-induced injury of human lens epithelial cells by up regulating VEGFA expression.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Hirokazu Kimura *Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.ORCID http://orcid.org/0000-0002-9835-6659
Ryota Sada *Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.ORCID http://orcid.org/0000-0003-3403-0542
Naoki Takada *Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.ORCID http://orcid.org/0000-0002-8953-1785
Akikazu HaradaDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.ORCID http://orcid.org/0000-0002-8123-652X
Yuichiro DokiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hidetoshi EguchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hideki YamamotoDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
Akira KikuchiDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan. akikuchi@molbiobc.med.osaka-u.ac.jp.ORCID http://orcid.org/0000-0003-3378-9522
The University of Osaka · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dickkopf1 (DKK1) is overexpressed in various cancers and promotes cancer cell proliferation by binding to cytoskeleton-associated protein 4 (CKAP4). However, the mechanisms underlying DKK1 expression are poorly understood. RNA sequence analysis revealed that expression of the transcription factor forkhead box M1 (FOXM1) and its target genes concordantly fluctuated with expression of DKK1 in pancreatic ductal adenocarcinoma (PDAC) cells. DKK1 knockdown decreased FOXM1 expression and vice versa in PDAC and esophageal squamous cell carcinoma (ESCC) cells. Inhibition of either the DKK1-CKAP4-AKT pathway or the ERK pathway suppressed FOXM1 expression, and simultaneous inhibition of both pathways showed synergistic effects. A FOXM1 binding site was identified in the 5'-untranslated region of the DKK1 gene, and its depletion decreased DKK1 expression and cancer cell proliferation. Clinicopathological and database analysis revealed that PDAC and ESCC patients who simultaneously express DKK1 and FOXM1 have a poorer prognosis. Multivariate analysis demonstrated that expression of both DKK1 and FOXM1 is the independent prognostic factor in ESCC patients. Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.

Indexed as

AdultAgedAged, 80 and overCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaFeedbackForkhead Box Protein M1Gene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsMiddle AgedPancreasPancreatic NeoplasmsDKK1 protein, humanForkhead Box Protein M1FOXM1 protein, humanIntercellular Signaling Peptides and Proteins

Identifiers

PMID34117362
PMCPMC8249240
OpenAlexW3170408830

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.