Open AccessThe adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling
Author(s) -
Zecchini Silvia,
Bombardelli Lorenzo,
Decio Alessandra,
Bianchi Marco,
Mazzarol Giovanni,
Sanguineti Fabio,
Aletti Giovanni,
Maddaluno Luigi,
Berezin Vladimir,
Bock Elisabeth,
Casadio Chiara,
Viale Giuseppe,
Colombo Nicoletta,
Giavazzi Raffaella,
Cavallaro Ugo
Publication year - 2011
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100152
Subject(s) - neural cell adhesion molecule , fibroblast growth factor receptor , cancer research , fibroblast growth factor , biology , cell adhesion , microbiology and biotechnology , receptor , cell , biochemistry , genetics
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.