Submitted Abstract
Metastasis is the primary cause of death from cancer. An early and critical step of the metastatic cascade is the acquisition by tumor cells of the ability to remodel the extracellular matrix (ECM) and migrate through the stromal environment 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 secrete matrix metalloproteinases (MMPs) that degrade the ECM to facilitate tumor cell dissemination and cancer progression. In the METASTALIM project we explore the functional and physical interaction between two cytoskeletal proteins which are specifically up-regulated in triple negative breast cancer cells and critically promote invadopodia formation and activity. Using a combination of cellular and molecular approaches, as well as relevant mouse models, we hope to demonstrate that targeting this axis represent a promising point of intervention to inhibit breast cancer invasion and metastasis.