a Immunofluorescence for FLAG (Merlin) or streptavidin in M10G meningioma cells expressing MerlinFLAG-APEX2 constructs after proximity-labelling. Representative of five biological replicates. Scale bar, 10 μm. b Heatmap of β-catenin biotinylation peptide intensity from proximity-labeling proteomic mass spectrometry as in (a) (n = 3/condition). c TOP-Flash Tcf/Lef luciferase reporter assay in M10GdCas9-KRAB meningioma cells expressing sgRNAs suppressing NF2 (sgNF2) with or without rescue of MerlinFLAG-APEX2 wildtype or cancer-associated missense constructs, n = 3. d Immunoblots for FLAG (Merlin) or β-catenin after biochemical fractionation of CH-157MN meningioma cells expressing MerlinFLAG-APEX2 rescue constructs. Immunoblots for calreticulin, α-tubulin, vimentin, Rb, or histone H3 mark membrane (M), cytoplasmic (Cp), cytoskeletal (Cs), nuclear (N), or chromatin fractions (Ch), respectively. Representative of six biological replicates. e TOP-Flash Tcf/Lef luciferase reporter assay in M10G meningioma cells expressing non-targeted control siRNAs (siNTC) or siRNAs suppressing β-catenin (siCTNNB1) with or without 24 h of Wnt3a treatment (100 ng/μl). Data are representative of four biological replicates. f–h TOP-Flash Tcf/Lef luciferase reporter assays in M10GdCas9-KRAB meningioma cells expressing non-targeted control sgRNAs (sgNTC) or sgNF2 with or without 24 h of Wnt3a treatment (100 ng/μl) in the presence or absence of β-catenin or Merlin overexpression or rescue. Data are representative of four biological replicates. f shows β-catenin overexpression fails to hyperactivate the Wnt pathway in the absence of Merlin. Data are representative of four biological replicates. g, h show Wnt stimulation is necessary for Merlin overexpression to hyperactivate the Wnt pathway. Data are representative of four biological replicates. Lines represent means, and error bars represent standard error of the means. **P ≤ 0.01, ***P ≤ 0.0001 (Student’s t test, one sided). Source data are provided as a Source Data file.