title: Nuclear GSK-3β segregation in desmoid-type fibromatosis.
abstract: OBJECTIVE
  Desmoid-type fibromatosis (DF) is a rare benign myofibroblastic neoplasm of the connective tissue that is unable to metastasize but is associated with a high local recurrence rate. Nuclear β-catenin is the most commonly used histological marker of DF; however, clinical and biological predictive markers guiding the treatment and follow-up of DF are still lacking. Normally, β-catenin is regulated by the cytoplasmic multiprotein complex of adenomatous polyposis coli (APC), axin, casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK-3β); this phosphorylates and degrades β-catenin, which would otherwise translocate to the nucleus. The aim of this study was to analyse the expression and localization of the β-catenin-protein complex of the Wnt pathway in cells isolated from DF patients.
  
  
  RESULTS
  We isolated cells from biopsies of DF patients, and demonstrated, by immunofluorescence and immunoblot analyses, that it is almost exclusively nuclear GSK-3β that colocalizes and interacts with β-catenin. The nuclear translocation of β-catenin and GSK-3β is not correlated with CTNNB1 mutations. In DF samples, the multiprotein complex is disrupted, as the cytoplasmic localization of APC and axin makes interaction with the nuclear β-catenin and GSK-3β impossible.
  
  
  CONCLUSIONS
  Our data suggest that GSK-3β is an additional DF marker with an important role in the aetiopathogenesis of this entity.
authors.affiliation: Genetics Unit, 'Mauro Baschirotto' Institute for Rare Diseases, Vicenza, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Meneghello
authors.forename: Bouchra
authors.initials: B
authors.lastname: Ousghir
authors.forename: Marco
authors.initials: M
authors.lastname: Rastrelli
authors.forename: Laura
authors.initials: L
authors.lastname: Anesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Sommariva
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Montesco
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
authors.forename: Uros
authors.initials: U
authors.lastname: Hladnik
authors.forename: Daniela
authors.initials: D
authors.lastname: Segat
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D018222:Desmoid Tumors / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3