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, α₃β₁ integrin and the gelatinolytic enzyme, seprase, exist as nonassociating membrane proteins. Type I collagen substratum induces the association of α₃β₁ integrin with seprase as a complex on invadopodia. The results show that α₃β₁ integrin is a docking protein for seprase to form functional invadopodia. In addition, α₅β₁ integrin may participate in the adhesion process necessary for invadopodial formation. Thus, α₃β₁ and α₅β₁ integrins play major organizational roles in the adhesion and formation of invadopodia, promoting invasive cell behavior.