Evidence map›Paper›PMID 29774524›Full record

ArticleThe Journal of pathology2018

αE-catenin is a candidate tumor suppressor for the development of E-cadherin-expressing lobular-type breast cancer.

Jolien S de Groot, Max Ak Ratze, Miranda van Amersfoort, Tanja Eisemann, Eva J Vlug, Mijanou T Niklaas, Suet-Feung Chin, Carlos Caldas, Paul J van Diest, Jos Jonkers and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

33 citing papers in PubMed, 50 citations in OpenAlex.

  1. Toward targeted therapeutics for lobular breast cancer.The Journal of clinical investigation · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025
    Review
  10. Insights into E-Cadherin Impairment inInternational journal of molecular sciences · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Hereditary Diffuse Gastric Cancer: A 2022 Update.Journal of personalized medicine · 2022
    Review
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

12 authors at 3 institutions in 2 countries.

Jolien S de GrootDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Max Ak RatzeDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Miranda van AmersfoortDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Tanja EisemannDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Eva J VlugDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Mijanou T NiklaasDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Suet-Feung ChinCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Carlos CaldasCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Paul J van DiestDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Jos JonkersDepartment of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-9264-9792
Johan de RooijDepartment of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Patrick Wb DerksenDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0003-0732-7762
University Medical Center Utrecht · NLUniversity of Cambridge · GBThe Netherlands Cancer Institute · NL

Funding

Cancer Research UK 16942
6 · The paper itself

Abstract

Although mutational inactivation of E-cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), approximately 10-15% of all ILCs retain membrane-localized E-cadherin despite the presence of an apparent non-cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α-catenin (CTNNA1) loss in the regulation of anchorage independence of non-invasive breast carcinoma. We found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto-lobular phenotypes. Further, inducible loss of α-catenin in mouse and human E-cadherin-expressing breast cancer cells led to atypical localization of E-cadherin, a rounded cell morphology, and anoikis resistance. Pharmacological inhibition experiments subsequently revealed that, similar to E-cadherin-mutant ILC, anoikis resistance induced by α-catenin loss was dependent on Rho/Rock-dependent actomyosin contractility. Finally, using a transplantation-based conditional mouse model, we demonstrate that inducible inactivation of α-catenin instigates acquisition of lobular features and invasive behavior. We therefore suggest that α-catenin represents a bona fide tumor suppressor for the development of lobular-type breast cancer and as such provides an alternative event to E-cadherin inactivation, adherens junction (AJ) dysfunction, and subsequent constitutive actomyosin contraction. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

Cell AdhesionActomyosinAdherens Junctionsalpha CateninAnimalsAnoikisAntigens, CDBreast NeoplasmsCadherinsCarcinoma, LobularCell ProliferationCell ShapeFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHumansActomyosinalpha CateninAntigens, CDCadherinsCDH1 protein, humanCdh1 protein, mouseCTNNA1 protein, humanCtnna1 protein, mouserho-Associated Kinasesrho GTP-Binding ProteinsTrp53 protein, mouseTumor Suppressor Protein p53Tumor Suppressor ProteinsE-cadherinlobular breast cancermouse modelRho/Rockα-catenin (CTNNA1)

Identifiers

PMID29774524
PMCPMC6055824
OpenAlexW2803358080

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.