A novel protease-docking function of integrin at invadopodia.
Invadopodia are membrane extensions of aggressive tumor cells that function in the activation of membrane-bound proteases occurring during tumor cell invasion. We explore a novel and provocative activity of integrins in docking proteases to sites of invasion, termed invadopodia. In the absence of collagen, alpha(3)beta(1) integrin and the gelatinolytic enzyme, seprase, exist as nonassociating membrane proteins. Type I collagen substratum induces the association of alpha(3)beta(1) integrin with seprase as a complex on invadopodia. The results show that alpha(3)beta(1) integrin is a docking protein for seprase to form functional invadopodia. In addition, alpha(5)beta(1) integrin may participate in the adhesion process necessary for invadopodial formation. Thus, alpha(3)beta(1) and alpha(5)beta(1) integrins play major organizational roles in the adhesion and formation of invadopodia, promoting invasive cell behavior.
Mueller
S C
SC
Lombardi Cancer Center and Department of Cell Biology, Georgetown University Medical Center, Washington, D. C. 20007, USA.
Ghersi
G
G
Akiyama
S K
SK
Sang
Q X
QX
Howard
L
L
Pineiro-Sanchez
M
M
Nakahara
H
H
Yeh
Y
Y
Chen
W T
WT
D000818:Animals; D000954:Antigens, Surface; D014408:Biomarkers, Tumor / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D010450:Endopeptidases; D005455:Fluorescent Antibody Technique; D018093:Gelatinases / Q000378:metabolism*; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D012697:Serine Endopeptidases; D014407:Tumor Cells, Cultured; D000099167:Fibroblast Activation Protein Alpha
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D003094:Collagen; D010450:Endopeptidases; D018093:Gelatinases; D039201:Integrin alpha3beta1; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha