Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor

Chiara Francavilla, Sébastien Loeffler, Daniele Piccini, Angelika Kren, Gerhard Christofori, Ugo Cavallaro

Research output: Contribution to journalArticle

Abstract

Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in the nervous system, yet NCAM is also expressed in non-neural tissues, in which its function has in most parts remained elusive. We have previously reported that NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether the interplay between NCAM and FGFR has any impact on the response of FGFR to its classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM-negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM was manipulated by means of transfection or RNAi technologies, respectively. The results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2 activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3 cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its high-affinity receptor in a competitive manner, providing the mechanisms for the NCAM-mediated suppression of FGF function. In this context, a small peptide that mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell proliferation. These findings point to NCAM as being a major regulator of FGF-FGFR interaction, thus introducing a novel type of control mechanism for FGFR activity and opening new therapeutic perspectives for those diseases characterized by aberrant FGFR function.

Original languageEnglish
Pages (from-to)4388-4394
Number of pages7
JournalJournal of Cell Science
Volume120
Issue number24
DOIs
Publication statusPublished - Dec 15 2007

Fingerprint

Neural Cell Adhesion Molecules
Fibroblast Growth Factors
Fibroblast Growth Factor Receptors
Cell-Matrix Junctions
NIH 3T3 Cells
Cell Proliferation
RNA Interference
Cell Adhesion
Nervous System
Transfection

Keywords

  • Fibroblast growth factor receptor
  • Neural cell adhesion molecule
  • Receptor binding
  • Signaling

ASJC Scopus subject areas

  • Cell Biology

Cite this

Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor. / Francavilla, Chiara; Loeffler, Sébastien; Piccini, Daniele; Kren, Angelika; Christofori, Gerhard; Cavallaro, Ugo.

In: Journal of Cell Science, Vol. 120, No. 24, 15.12.2007, p. 4388-4394.

Research output: Contribution to journalArticle

Francavilla, C, Loeffler, S, Piccini, D, Kren, A, Christofori, G & Cavallaro, U 2007, 'Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor', Journal of Cell Science, vol. 120, no. 24, pp. 4388-4394. https://doi.org/10.1242/jcs.010744
Francavilla, Chiara ; Loeffler, Sébastien ; Piccini, Daniele ; Kren, Angelika ; Christofori, Gerhard ; Cavallaro, Ugo. / Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor. In: Journal of Cell Science. 2007 ; Vol. 120, No. 24. pp. 4388-4394.
@article{675edd0de8a347df8f6088b0167a3291,
title = "Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor",
abstract = "Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in the nervous system, yet NCAM is also expressed in non-neural tissues, in which its function has in most parts remained elusive. We have previously reported that NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether the interplay between NCAM and FGFR has any impact on the response of FGFR to its classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM-negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM was manipulated by means of transfection or RNAi technologies, respectively. The results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2 activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3 cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its high-affinity receptor in a competitive manner, providing the mechanisms for the NCAM-mediated suppression of FGF function. In this context, a small peptide that mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell proliferation. These findings point to NCAM as being a major regulator of FGF-FGFR interaction, thus introducing a novel type of control mechanism for FGFR activity and opening new therapeutic perspectives for those diseases characterized by aberrant FGFR function.",
keywords = "Fibroblast growth factor receptor, Neural cell adhesion molecule, Receptor binding, Signaling",
author = "Chiara Francavilla and S{\'e}bastien Loeffler and Daniele Piccini and Angelika Kren and Gerhard Christofori and Ugo Cavallaro",
year = "2007",
month = "12",
day = "15",
doi = "10.1242/jcs.010744",
language = "English",
volume = "120",
pages = "4388--4394",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "24",

}

TY - JOUR

T1 - Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor

AU - Francavilla, Chiara

AU - Loeffler, Sébastien

AU - Piccini, Daniele

AU - Kren, Angelika

AU - Christofori, Gerhard

AU - Cavallaro, Ugo

PY - 2007/12/15

Y1 - 2007/12/15

N2 - Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in the nervous system, yet NCAM is also expressed in non-neural tissues, in which its function has in most parts remained elusive. We have previously reported that NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether the interplay between NCAM and FGFR has any impact on the response of FGFR to its classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM-negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM was manipulated by means of transfection or RNAi technologies, respectively. The results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2 activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3 cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its high-affinity receptor in a competitive manner, providing the mechanisms for the NCAM-mediated suppression of FGF function. In this context, a small peptide that mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell proliferation. These findings point to NCAM as being a major regulator of FGF-FGFR interaction, thus introducing a novel type of control mechanism for FGFR activity and opening new therapeutic perspectives for those diseases characterized by aberrant FGFR function.

AB - Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in the nervous system, yet NCAM is also expressed in non-neural tissues, in which its function has in most parts remained elusive. We have previously reported that NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether the interplay between NCAM and FGFR has any impact on the response of FGFR to its classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM-negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM was manipulated by means of transfection or RNAi technologies, respectively. The results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2 activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3 cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its high-affinity receptor in a competitive manner, providing the mechanisms for the NCAM-mediated suppression of FGF function. In this context, a small peptide that mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell proliferation. These findings point to NCAM as being a major regulator of FGF-FGFR interaction, thus introducing a novel type of control mechanism for FGFR activity and opening new therapeutic perspectives for those diseases characterized by aberrant FGFR function.

KW - Fibroblast growth factor receptor

KW - Neural cell adhesion molecule

KW - Receptor binding

KW - Signaling

UR - http://www.scopus.com/inward/record.url?scp=38349006468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349006468&partnerID=8YFLogxK

U2 - 10.1242/jcs.010744

DO - 10.1242/jcs.010744

M3 - Article

C2 - 18042627

AN - SCOPUS:38349006468

VL - 120

SP - 4388

EP - 4394

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 24

ER -