Growth factor and integrin signaling promote coordinated actin polymerization at the leading edge of migrating cells. Polymerized actin assembles in complex three-dimensional multiprotein structures with specific biological functions, including membrane protrusion and force generation, adhesion and traction or membrane invagination and endocytic uptake. When tumor cells migrate and invade, they rely on these dynamic structures. We investigate molecular regulators in MB tumor cells that orchestrate actin polymerization and search for ways to specifically interfere with those processes that are necessary for tumor cell invasion. We specifically focus on functions of the Ser/Thr kinase MAP4K4 and its up-stream regulators and downstream effectors. Using biochemical and cell biological approaches, we have identified MAP4K4-controled regulators of actin dynamics and endocytic turnover and now address how these proteins can be specifically blocked.

bFGF-stimulated MB ERK-SKARS cells