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Cited by 363Neurofibromatosis and Schwannoma CasesHER2/EGFR in Cancer ResearchProtein Kinase Regulation and GTPase Signaling

Contact-dependent inhibition of EGFR signaling by Nf2/Merlin

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Curto, Marcello, Cole, Banumathi K., Lallemand, Dominique, Liu, Ching-Hui, McClatchey, Andrea I.·2007·The Journal of Cell Biology
DOI 10.1083/jcb.200703010PMC PMC2064288
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Abstract

The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a membrane/cytoskeleton-associated protein that mediates contact-dependent inhibition of proliferation. Here we show that upon cell–cell contact Merlin coordinates the processes of adherens junction stabilization and negative regulation of epidermal growth factor receptor (EGFR) signaling by restraining the EGFR into a membrane compartment from which it can neither signal nor be internalized. In confluent Nf2−/− cells, EGFR activation persists, driving continued proliferation that is halted by specific EGFR inhibitors. These studies define a new mechanism of tumor suppression, provide mechanistic insight into the poorly understood phenomenon of contact-dependent inhibition of proliferation, and suggest a therapeutic strategy for NF2-mutant tumors.

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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 [46]

    The Results (page unavailable) show that E-cadherin associates with EGFR in cultured cells and that disrupting cadherin-based adhesion increases EGFR signaling. But the reported association depends on NHE-RF1, and the paper attributes contact-dependent EGFR inhibition to Merlin; it does not show that E-cadherin itself directly interacts with or independently regulates EGFR. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 60

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Cited by

Sorted by citations

Authors
Curto, M., Cole, B. K., Lallemand, D., Liu, C.-H., & McClatchey, A. I.
Affiliations
Harvard University (US)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2007-06-04
Volume
177
Issue
5
Pages
893-903
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200703010
PMC
PMC2064288
OpenAlex
W2114550587
Cited by
363
References
0
Citations by year
2026: 6 · 2025: 12 · 2024: 12 · 2023: 10 · 2022: 17 · 2021: 12 · 2020: 11 · 2019: 16 · 2018: 21 · 2017: 22 · 2016: 15 · 2015: 24 · 2014: 26 · 2013: 20 · 2012: 33
FWCI
15.68
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Merlin, neurofibromatosis type 2, EGFR signaling, adherens junctions, tumor suppression, cell-cell contact, EGFR internalization, EGFR inhibitors
MeSH terms
Animals, Cell Adhesion, Cell Line, Models, Biological, Phosphoproteins, Signal Transduction, Protein Structure, Tertiary, Sodium-Hydrogen Exchangers, Neurofibromin 2, Cell Proliferation, Mice, ErbB Receptors

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