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 docki ng proteases to sites of invasion, termed invadopodia. In the absence of co llagen, alpha(3)beta(1) integrin and the gelatinolytic enzyme, seprase, exi st as nonassociating membrane proteins. Type I collagen substratum induces the association of alpha(3)beta(1) integrin with seprase as a complex on in vadopodia. The results show that alpha(3)beta(1) integrin is a docking prot ein for seprase to form functional invadopodia, In addition, alpha(5)beta(1 ) integrin may participate in the adhesion process necessary for invadopodi al formation. Thus, alpha(3)beta(1) and alpha(5)beta(1) integrins play majo r organizational roles in the adhesion and formation of invadopodia, promot ing invasive cell behavior.