Inhibition of breast cancer metastasis by targeting critical cytoskeletal components of invadopodia

Metastasis is the primary cause of death from cancer. An early and critical step of the metastatic cascade is theacquisition by tumor cells of the ability to remodel the extracellular matrix (ECM) and migrate through the stromalenvironment and tissue barriers. At the subcellular level, this ability is associated with actin-rich, fingerlike,membrane protrusions termed invadopodia. The primary function of invadopodia is to concentrate and secretematrix metalloproteinases (MMPs) that degrade the ECM to facilitate tumor cell dissemination and cancerprogression. In the METASTALIM project we explore the functional and physical interaction between twocytoskeletal proteins which are specifically up-regulated in triple negative breast cancer cells and critically promoteinvadopodia formation and activity. Using a combination of cellular and molecular approaches, as well as relevantmouse models, we hope to demonstrate that targeting this axis represent a promising point of intervention to inhibitbreast cancer invasion and metastasis.