Nuclear GSK-3β segregation in desmoid-type fibromatosis

Cristiana Meneghello, Bouchra Ousghir, Marco Rastrelli, Laura Anesi, Antonio Sommariva, Maria Cristina Montesco, Carlo Riccardo Rossi, Uros Hladnik, Daniela Segat

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: 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. Methods and 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.

Original languageEnglish
Pages (from-to)1098-1108
Number of pages11
JournalHistopathology
Volume62
Issue number7
DOIs
Publication statusPublished - Jun 2013

Keywords

  • β-catenin
  • Axin
  • Cyclin D1
  • Desmoid-type fibromatosis
  • GSK-3β
  • Wnt pathway

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Nuclear GSK-3β segregation in desmoid-type fibromatosis'. Together they form a unique fingerprint.

Cite this