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Cited by 20Protein Kinase Regulation and GTPase SignalingCell Adhesion Molecules ResearchCellular Mechanics and Interactions

Cooperation of distinct Rac-dependent pathways to stabilise E-cadherin adhesion

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Erasmus, Jennifer C., Welsh, Natalie J., Braga, Vania M.M.·2015·Cellular Signalling
DOI 10.1016/j.cellsig.2015.04.014PMC PMC4508347
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Abstract

The precise mechanisms via which Rac1 is activated by cadherin junctions are not fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR signalling, but how EGFR does so is unclear. To address which activator could mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs, SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and led to fragmented localization of E-cadherin at cadherin contacts. In contrast, depletion of another EGFR family member, ErbB3, did not interfere with either process. DOCK180 RNAi, but not SOS1, prevented E-cadherin-induced Rac1 activation. However, in a strong divergence from EGFR RNAi phenotype, DOCK180 depletion did not perturb actin recruitment or cadherin localisation at junctions. Rather, reduced DOCK180 levels impaired the resistance to mechanical stress of pre-formed cell aggregates. Thus, within the same cell type, EGFR and DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate cellular events that cooperate to stabilise junctions.

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  • E-cadherin itself was shown to interact with and regulate EGFR in vitro.

    “Along the same lines, E-cadherin itself was shown to interact with and regulate EGFR in vitro46–49.”

    From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [49]

    The Results section on EGFR and junction-dependent Rac activation reports that EGFR co-precipitates with E-cadherin in keratinocytes, supporting an association in vitro. The Introduction and Discussion describe EGFR-dependent signalling following E-cadherin contact formation, but the cited passages do not show that E-cadherin regulates EGFR itself. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Erasmus, J. C., Welsh, N. J., & Braga, V. M. M.
Affiliations
Imperial College London (GB)
Corresponding author
Braga, Vania M.M.
ORCID
Venue
Cellular Signalling
Publisher
Elsevier BV
Published
2015-09
Volume
27
Issue
9
Pages
1905-1913
ISSN
0898-6568 (ISSN-L)
DOI
10.1016/j.cellsig.2015.04.014
PMC
PMC4508347
OpenAlex
W1861852546
Cited by
20
References
0
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 1 · 2015: 1
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular Signalling (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust
  • Cancer Research UK (C1282/A11980, C1282/A5960/G18481)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
Rac1, E-cadherin, cell adhesion, EGFR signaling, DOCK180, SOS1, HER3, keratinocytes, mechanical stress resistance, cell aggregates, actin recruitment, junction stability
MeSH terms
Cell Adhesion, Cells, Cultured, Humans, Signal Transduction, Keratinocytes, Cadherins, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Receptor, ErbB-3, RNA Interference

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