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J Cell Biol. 2007 Jun 4;177(5):893-903.

Contact-dependent inhibition of EGFR signaling by Nf2/Merlin.

Author information

  • 1MGH Center for Cancer Research, Harvard Medical School Department of Pathology, Charlestown, MA 02129, USA.

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.

PMID:
17548515
PMCID:
PMC2064288
DOI:
10.1083/jcb.200703010
[PubMed - indexed for MEDLINE]
Free PMC Article
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