Cell-ECM Interactions Promote Invadopodia Maturation

Abstract

These studies tested the hypothesis that cell-extracellular matrix (ECM) interactions promote the maturation of invadopodia to fully functional structures. I demonstrate that invadopodia-associated ECM degradation is modulated by substrate stiffness and density. Overexpression of the mechanosensing proteins FAK and p130Cas can promote the invadopodial response to stiffness. In addition, I investigated the role of integrins as promoters of invadopodia formation and function. Adhesion proteins were found to distinctly localize in ring-like structures around invadopodia. Blocking RGD-binding integrin attachment to the ECM or knockdown of integrin-linked kinase specifically affected cellular ECM degradation by reducing MT1-MMP recruitment to invadopodia. This process apparently involves downstream recruitment of the scaffold protein IQGAP. These data support a model in which cell-ECM interactions specifically promote the maturation stage of invadopodia to promote matrix degradation.