Evidence map›Paper›PMID 23815780›Full record

ArticleBMC cancer2013

Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer.

Dawn T Bravo, Yi-Lin Yang, Kristopher Kuchenbecker, Ming-Szu Hung, Zhidong Xu, David M Jablons, Liang You

Abstract read
In one paragraph

Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
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

23 citing papers in PubMed.

  1. Article
  2. Review
  3. Wnt signaling and tumors (Review).Molecular and clinical oncology · 2024
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Frizzled Receptors as Potential Therapeutic Targets in Human Cancers.International journal of molecular sciences · 2018
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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

7 authors.

Dawn T BravoDepartment of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
Yi-Lin Yang
Kristopher Kuchenbecker
Ming-Szu Hung
Zhidong Xu
David M Jablons
Liang You

Funding

The Role of Cul4A in Genome Stability and Cancer DevelopmentR01CA140654 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOU, LIANG · 2010 to 2014
$1.5M
Roles of Wnt Receptors (Frizzled) in Prostate CancerF32CA119636 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BRAVO, DAWN T · 2006 to 2008
$145k
NCI NIH HHS F32CA119636NCI NIH HHS R01 CA140654NCI NIH HHS R01CA140654-01A1
6 · The paper itself

Abstract

backgroundWnt-2 plays an oncogenic role in cancer, but which Frizzled receptor(s) mediates the Wnt-2 signaling pathway in lung cancer remains unclear. We sought to (1) identify and evaluate the activation of Wnt-2 signaling through Frizzled-8 in non-small cell lung cancer, and (2) test whether a novel expression construct dominant negative Wnt-2 (dnhWnt-2) reduces tumor growth in a colony formation assay and in a xenograft mouse model.

methodsSemi-quantitative RT-PCR was used to identify the expression of Wnt-2 and Frizzled-8 in 50 lung cancer tissues from patients. The TCF reporter assay (TOP/FOP) was used to detect the activation of the Wnt canonical pathway in vitro. A novel dnhWnt-2 construct was designed and used to inhibit activation of Wnt-2 signaling through Frizzled-8 in 293T, 293, A549 and A427 cells and in a xenograft mouse model. Statistical comparisons were made using Student's t-test.

resultsAmong the 50 lung cancer samples, we identified a 91% correlation between the transcriptional increase of Wnt-2 and Frizzled-8 (p<0.05). The Wnt canonical pathway was activated when both Wnt-2 and Frizzled-8 were co-expressed in 293T, 293, A549 and A427 cells. The dnhWnt-2 construct we used inhibited the activation of Wnt-2 signaling in 293T, 293, A549 and A427 cells, and reduced the colony formation of NSCLC cells when β-catenin was present (p<0.05). Inhibition of Wnt-2 activation by the dnhWnt-2 construct further reduced the size and mass of tumors in the xenograft mouse model (p<0.05). The inhibition also decreased the expression of target genes of Wnt signaling in these tumors.

conclusionsWe demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in NSCLC cells. A novel dnhWnt-2 construct significantly inhibits Wnt-2 signaling, reduces colony formation of NSCLC cells in vitro and tumor growth in a xenograft mouse model. The dnhWnt-2 construct may provide a new therapeutic avenue for targeting the Wnt pathway in lung cancer.

Indexed as

AnimalsBlotting, WesternCarcinoma, Non-Small-Cell LungDisease Models, AnimalFemaleFrizzled ReceptorsHumansLigandsLung NeoplasmsMiceMice, NudeReverse Transcriptase Polymerase Chain ReactionSignal TransductionWnt2 ProteinXenograft Model Antitumor AssaysFrizzled ReceptorsLigandsWnt2 Protein

Identifiers

PMID23815780
PMCPMC3707790

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Registered trials

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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.