Invadopodia are actin-based membrane protrusions with high proteolytic activity that are thought to have an important role in cancer-cell invasion and intravasation. However, questions have remained about the formation and precise function of these structures during metastasis. On page , John Condeelis and colleagues extend their previous observation that neural Wiskott–Aldrich syndrome protein (N-WASP) is an essential component of invadopodia by discovering that N-WASP-mediated formation of invadopodia is required for the process of invasion and intravasation during breast cancer metastasis. Reducing the activity or expression of N-WASP in rat mammary adenocarcinoma cells leads to a reduction in the number and proteolytic activity of invadopodia in vitro, and decreases the invasive ability of the cells in vivo. The lack of functional N-WASP does not affect tumour size, but decreases the number of circulating tumour cells and the formation of metastasis. Primary tumour cells without functional N-WASP are also more round, less polarised, form fewer protrusions and are less mobile than cancer cells that express N-WASP. In addition, cells without N-WASP lack the ability to efficiently degrade collagen I at the invasive edge and in areas enriched with blood vessels. The actin nucleator N-WASP, thus, has a crucial role in driving the formation of proteolytic invadopodia and cancer cell metastasis.
