Evidence map›Paper›PMID 25023701›Full record

ArticleOncogene2015

DACT2 is a functional tumor suppressor through inhibiting Wnt/β-catenin pathway and associated with poor survival in colon cancer.

S Wang, Y Dong, Y Zhang, X Wang, L Xu, S Yang, X Li, H Dong, L Xu, L Su and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. CUT&TIME captures the history of open chromatin in developing neurons.bioRxiv : the preprint server for biology · 2025
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  3. P2YActa pharmaceutica Sinica. B · 2025
    Article
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  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Cell journal · 2022
    Article
  12. The Role of DACT Family Members in Tumorigenesis and Tumor Progression.International journal of biological sciences · 2022
    Review
  13. Norrie disease protein is essential for cochlear hair cell maturation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Investigating the methylation status ofMolecular biology research communications · 2019
    Article
  19. Epigenetically Silenced Candidate Tumor Suppressor Genes in Prostate Cancer: Identified by Modeling Methylation Stratification and Applied to Progression Prediction.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019
    Article
  20. 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

15 authors at 4 institutions in 1 country.

S Wang1] Research Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China [2] Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
Y Dong1] Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China [2] Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
Y ZhangSchool of Medicine, School of Life Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing, China.
X WangInstitute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
L XuInstitute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
S YangSchool of Medicine, School of Life Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing, China.
X LiInstitute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
H DongResearch Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
L XuResearch Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
L SuResearch Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
S S M NgDepartment of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
Z ChangSchool of Medicine, School of Life Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing, China.
J J SungInstitute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
X ZhangResearch Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
J YuInstitute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
Chinese University of Hong Kong, Shenzhen · CNUniversity of Science and Technology Beijing · CNTsinghua University · CNChinese University of Hong Kong · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dapper homolog (DACT) 2 is one of the Dact gene family members, which are important modulators of Wnt signaling pathway. We aim to clarify its epigenetic inactivation, biological function and clinical implication in colon cancer. DACT2 was silenced in five out of eight colon cancer cell lines, but robustly expressed in normal colon tissues. The loss of DACT2 expression was regulated by promoter hypermethylation. Restoring DACT2 expression in colon cancer cell lines suppressed tumor cell growth by inducing cell apoptosis and inhibiting cell proliferation both in vitro and in vivo. Moreover, DACT2 overexpression effectively reduced lung metastasis of colon cancer cells in nude mice. These effects by DACT2 were attributed to inhibition of Wnt/β-catenin signaling. Reexpression of DACT2 significantly suppressed the transcriptional activity of both wild-type β-catenin and degradation-resistant form mutant β-catenin (S33Y). DACT2 could actively shuttle into and out of nuclei, with its predominant steady-state localization in the cytoplasm dependent on its nuclear export signal. Co-immunoprecipitation results indicated that DACT2 strongly associated β-catenin as well as lymphoid enhancer-binding factor 1 (LEF1) and directly disrupted the formation of the β-catenin-LEF1 complex in the nucleus. Whereas in the cytoplasm, DACT2 restored junctional localization of E-cadherin-β-catenin complexes and prevented β-catenin nuclear translocation through direct interaction with β-catenin. DACT2 methylation was detected in 43.3% (29/67) of colon cancer tissues, but none in normal controls. Multivariate analysis revealed that patients with DACT2 methylation had a significant decrease in overall survival (P=0.006). Kaplan-Meier survival curves showed that DACT2 methylation was significantly associated with shortened survival in stage I-III colon cancer patients. In conclusion, DACT2 acts as a functional tumor suppressor in colon cancer through inhibiting Wnt/β-catenin signaling. Its methylation at early stages of colon carcinogenesis is an independent prognostic factor.

Indexed as

Gene Expression Regulation, NeoplasticWnt Signaling PathwayActive Transport, Cell NucleusAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAmino Acid SubstitutionAnimalsbeta CateninCaco-2 CellsCadherinsCarrier ProteinsCell NucleusColonic NeoplasmsDisease-Free SurvivalAdaptor Proteins, Signal Transducingbeta CateninCadherinsCarrier ProteinsDACT2 protein, humanLEF1 protein, humanLymphoid Enhancer-Binding Factor 1Neoplasm ProteinsNuclear Localization SignalsTumor Suppressor Proteins

Identifiers

PMID25023701
PMCPMC4761644
OpenAlexW2039486119

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.