Faciogenital Dysplasia Protein Fgd1 Regulates Invadopodia Biogenesis and Extracellular Matrix Degradation and Is Up-regulated in Prostate and Breast Cancer

Cancer Research - Tập 69 Số 3 - Trang 747-752 - 2009
Inmaculada Ayala1, Giada Giacchetti1, Giusi Caldieri1, Francesca Attanasio1, Stefania Mariggiò2, Stefano Tetè3, Roman Polishchuk4, Vincent Castronovo5, Roberto Buccione1
11Tumor Cell Invasion Laboratory,
22Cell Regulation Laboratory, and
34Department of Oral Sciences, University “G. D'Annunzio”, Chieti, Italy; and
43Membrane Sorting and Biogenesis Unit, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy;
55Metastases Research Laboratory, Giga-Cancer, University of Liege, Liege, Belgium

Tóm tắt

Abstract 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. [Cancer Res 2009;69(3):747–52]

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Cancer Research

Tập 69 Số 3

747-752

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