TY - JOUR
T1 - Diaphanous-related formins are required for invadopodia formation and invasion of breast tumor cells
AU - Lizárraga, Floria
AU - Poincloux, Renaud
AU - Romão, Maryse
AU - Montagnac, Guillaume
AU - Le Dez, Gaëlle
AU - Bonne, Isabelle
AU - Rigaill, Guillem
AU - Raposo, Graça
AU - Chavrier, Philippe
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Proteolytic degradation of the extracellular matrix by metastatic tumor cells is initiated by the formation of invadopodia, i.e., actin-driven filopodia-like membrane protrusions endowed with matrix-degradative activity. A signaling cascade involving neural Wiskott-Aldrich syndrome protein and the Arp2/3 actin nucleating complex is involved in actin assembly at invadopodia. Yet, the mechanism of invadopodia formation is poorly understood. Based on their role as actin nucleators in cytoskeletal rearrangements, including filopodia formation, we examined the function of Diaphanous-related formins (DRF) in invadopodia formation and invasion by breast tumor cells. Using small interfering RNA silencing of protein expression in highly invasive MDA-MB-231 breast adenocarcinoma cells, we show that three members of the DRF family (DRF1-DRF3) are required for invadopodia formation and two-dimensional matrix proteolysis. We also report that invasion of a three-dimensional Matrigel matrix involves filopodia-like protrusions enriched for invadopodia! proteins, including membrane type 1 matrix metalloproteinase, which depend on DRFs for their formation. These data identify DRFs as critical components of the invasive apparatus of tumor cells in two-dimensional and three-dimensional matrices and suggest that different types of actin nucleators cooperate during the formation of inva-dopodia.
AB - Proteolytic degradation of the extracellular matrix by metastatic tumor cells is initiated by the formation of invadopodia, i.e., actin-driven filopodia-like membrane protrusions endowed with matrix-degradative activity. A signaling cascade involving neural Wiskott-Aldrich syndrome protein and the Arp2/3 actin nucleating complex is involved in actin assembly at invadopodia. Yet, the mechanism of invadopodia formation is poorly understood. Based on their role as actin nucleators in cytoskeletal rearrangements, including filopodia formation, we examined the function of Diaphanous-related formins (DRF) in invadopodia formation and invasion by breast tumor cells. Using small interfering RNA silencing of protein expression in highly invasive MDA-MB-231 breast adenocarcinoma cells, we show that three members of the DRF family (DRF1-DRF3) are required for invadopodia formation and two-dimensional matrix proteolysis. We also report that invasion of a three-dimensional Matrigel matrix involves filopodia-like protrusions enriched for invadopodia! proteins, including membrane type 1 matrix metalloproteinase, which depend on DRFs for their formation. These data identify DRFs as critical components of the invasive apparatus of tumor cells in two-dimensional and three-dimensional matrices and suggest that different types of actin nucleators cooperate during the formation of inva-dopodia.
UR - http://www.scopus.com/inward/record.url?scp=66149139847&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-08-3709
DO - 10.1158/0008-5472.CAN-08-3709
M3 - Article
C2 - 19276357
AN - SCOPUS:66149139847
SN - 0008-5472
VL - 69
SP - 2792
EP - 2800
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -