Evidence map›Paper›PMID 10439038›Full record

ArticleOncogene1999

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.

G Handschuh, S Candidus, B Luber, U Reich, C Schott, S Oswald, H Becke, P Hutzler, W Birchmeier, H Höfler and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.2field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.

  1. Preemptive surgery for premalignant foregut lesions.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2009
    Pooled it
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  10. Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021
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  11. Review
  12. Genes · 2020
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  13. Article
  14. Article
  15. Review
  16. Functions of EpCAM in physiological processes and diseases (Review).International journal of molecular medicine · 2018
    Review
  17. Article
  18. Article
  19. Article
  20. A protein and mRNA expression-based classification of gastric cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2016
    Article

5 more citing papers are in PubMed but not listed here.

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.

G HandschuhGSF-Forschungszentrum für Umwelt and Gesundheit, Institut für Pathologie, Neuherberg, Germany.
S Candidus
B Luber
U Reich
C Schott
S Oswald
H Becke
P Hutzler
W Birchmeier
H Höfler
K F Becker
Klinikum rechts der Isar · DETechnical University of Munich · DEMax Delbrück Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A major function of the cell-to-cell adhesion molecule E-cadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin deficiency in tumours leads to changes in cell morphology and motility, so that E-cadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that affect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L fibroblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing E-cadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin filaments were drastically reduced. MDA-MB-435S cells with initial calcium-dependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply affect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations affecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diffuse type-gastric carcinomas.

Indexed as

Cell AdhesionCell MovementMutationActinsAnimalsCadherinsExonsFibroblastsFluorescent Antibody TechniqueHumansMammary Neoplasms, AnimalMiceMicroscopy, ConfocalModels, GeneticPoint MutationStomach NeoplasmsActinsCadherins

Identifiers

PMID10439038
OpenAlexW1967599173

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.