biostudies-literatureUnknown177(5)Curto MThe 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.The Journal of cell biology893-903https://www.ebi.ac.uk/biostudies/studies/S-EPMC2064288biostudies-literatureContact-dependent inhibition of EGFR signaling by Nf2/Merlin.PMC2064288Liu CHLallemand DCurto MMcClatchey AICole BKfalseContact-dependent inhibition of EGFR signaling by Nf2/Merlin.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.2007-01-01T00:00:00Z2007 Jun2024-11-12T21:35:38.307Z2019-03-26T23:02:24ZS-EPMC20642881754851510.1083/jcb.200703010