Evidence map›Paper›PMID 23752190›Full record

ArticleOncogene2014

Desmoglein 3 promotes cancer cell migration and invasion by regulating activator protein 1 and protein kinase C-dependent-Ezrin activation.

L Brown, A Waseem, I N Cruz, J Szary, E Gunic, T Mannan, M Unadkat, M Yang, F Valderrama, E A O'Toole and 1 more

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In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Desmosomal Cadherins in Health and Disease.Annual review of pathology · 2022
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Observational
  18. Article
  19. Article
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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

11 authors at 3 institutions in 1 country.

L BrownQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
A WaseemQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
I N CruzDepartment of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, London, UK.
J SzaryQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
E GunicQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
T MannanQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
M UnadkatQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
M YangDepartment of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, London, UK.
F ValderramaDivision of Biomedical Sciences, St George's, University of London, Cranmer Terrace, London, UK.
E A O'TooleQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Cutaneous Research, Blizard Institute, London, UK.
H WanQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, London, UK.
Queen Mary University of London · GBUniversity College London · GBSt George's, University of London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Desmoglein 3 (Dsg3), the pemphigus vulgaris antigen, has recently been shown to be upregulated in squamous cell carcinoma (SCC) and has been identified as a good tumor-specific marker for clinical staging of cervical sentinel lymph nodes in head and neck SCC. However, little is known about its biological function in cancer. The actin-binding protein Ezrin and the activator protein 1 (AP-1) transcription factor are implicated in cancer progression and metastasis. Here, we report that Dsg3 regulates the activity of c-Jun/AP-1 as well as protein kinase C (PKC)-mediated phosphorylation of Ezrin-Thr567, which contributes to the accelerated motility of cancer cells. Ectopic expression of Dsg3 in cancer cell lines caused enhanced phosphorylation at Ezrin-Thr567 with concomitant augmented membrane protrusions, cell spreading and invasive phenotype. We showed that Dsg3 formed a complex with Ezrin at the plasma membrane that was required for its proper function of interacting with F-actin and CD44 as Dsg3 knockdown impaired these associations. The increased Ezrin phosphorylation in Dsg3-overexpressing cells could be abrogated substantially by various pharmacological inhibitors for Ser/Thr kinases, including PKC and Rho kinase that are known to activate Ezrin. Furthermore, a marked increase in c-Jun S63 phosphorylation, among others, was found in Dsg3-overexpressing cells and the activation of c-Jun/AP-1 was further supported by a luciferase reporter assay. Taken together, our study identifies a novel Dsg3-mediated c-Jun/AP-1 regulatory mechanism and PKC-dependent Ezrin phosphorylation that could be responsible for Dsg3-associated cancer metastasis.

Indexed as

Cell MovementCell Line, TumorCell Surface ExtensionsCytoskeletal ProteinsDesmoglein 3EzrinHumansNeoplasm InvasivenessNeoplasmsPhosphorylationProtein Kinase CProto-Oncogene Proteins c-junTranscription Factor AP-1Cytoskeletal ProteinsDesmoglein 3DSG3 protein, humanEzrinProtein Kinase CProto-Oncogene Proteins c-junTranscription Factor AP-1

Identifiers

PMID23752190
OpenAlexW1981417550

What OpenQuestion holds

Textmetadata
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.