Speaker
Description
Metastatic tumor cells breach the barriers posed by the basement membrane, the interstitial connective tissue and the blood vessel wall in the so-called metastatic cascade. For invasion, both adhesion to the extracellular matrix and a spatially matched proteolysis of the extracellular matrix are essential. Therefore, invasive cancer cells form actin-rich protrusions on which β1 integrins and MMP14 are coupled both structurally and functionally to allow a tumor cell to adhere to and also to degrade extracellular matrix molecules. Hence, a combined inhibition of adhesion and/or protease activity may reduce the invasive properties of tumor cells. In order to analyze the MMP14 activity in invadopodia, Förster resonance energy transfer (FRET) probes are generated. Bifunctional compounds with specific integrin-and MMP14-targeting domains are designed to elucidate the structural and functional link and to suppress the barrier-breaching invadopodia activity.
