The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

Silvia Zecchini, Lorenzo Bombardelli, Alessandra Decio, Marco Bianchi, Giovanni Mazzarol, Fabio Sanguineti, Giovanni Aletti, Luigi Maddaluno, Vladimir Berezin, Elisabeth Bock, Chiara Casadio, Giuseppe Viale, Nicoletta Colombo, Raffaella Giavazzi, Ugo Cavallaro

Research output: Contribution to journalArticle

Abstract

Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR interplay with a monoclonal antibody abolishes the metastatic dissemination of EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target.

Original languageEnglish
Pages (from-to)480-494
Number of pages15
JournalEMBO Molecular Medicine
Volume3
Issue number8
DOIs
Publication statusPublished - Aug 2011

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Keywords

  • Fibroblast growth factor receptor
  • Neural cell adhesion molecule
  • Ovarian carcinoma
  • Signalling
  • Tumour progression

ASJC Scopus subject areas

  • Molecular Medicine

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