Article (Scientific journals)
Faciogenital dysplasia protein Fgd1 regulates invadopodia biogenesis and extracellular matrix degradation and is up-regulated in prostate and breast cancer.
Ayala, Inmaculada; Giacchetti, Giada; Caldieri, Giusi et al.
2009In Cancer Research, 69 (3), p. 747-52
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Keywords :
Cdc42; invasion; invadopodia; tumorigenesis
Abstract :
[en] Invadopodia are proteolytically active membrane protrusions that extend from the ventral surface of invasive tumoral cells grown on an extracellular matrix (ECM). The core machinery controlling invadopodia biogenesis is regulated by the Rho GTPase Cdc42. To understand the upstream events regulating invadopodia biogenesis, we investigated the role of Fgd1, a Cdc42-specific guanine nucleotide exchange factor. Loss of Fgd1 causes the rare inherited human developmental disease faciogenital dysplasia. Here, we show that Fgd1 is required for invadopodia biogenesis and ECM degradation in an invasive cell model and functions by modulation of Cdc42 activation. We also find that Fgd1 is expressed in human prostate and breast cancer as opposed to normal tissue and that expression levels matched tumor aggressiveness. Our findings suggest a central role for Fgd1 in the focal degradation of the ECM in vitro and, for the first time, show a connection between Fgd1 and cancer progression, proposing that it might function during tumorigenesis.
Research center :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Ayala, Inmaculada
Giacchetti, Giada
Caldieri, Giusi
Attanasio, Francesca
Mariggio, Stefania
Tete, Stefano
Polishchuk, Roman
Castronovo, Vincenzo ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases
Buccione, Roberto
Language :
English
Title :
Faciogenital dysplasia protein Fgd1 regulates invadopodia biogenesis and extracellular matrix degradation and is up-regulated in prostate and breast cancer.
Publication date :
2009
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland
Volume :
69
Issue :
3
Pages :
747-52
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
AIRC - Associazione Italiana per la Ricerca sul Cancro [IT]
EC - European Commission [BE]
Fondazione Cassa di Resparmio della Provincia di Teramo [IT]
Ministero della Salute [IT]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Calogero Musarra Foundation
Funding number :
European commission (LSHC-CT-2004-5030489)
Available on ORBi :
since 28 September 2009

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