Model for invadopodia formation and maturation. (A) Stages of BM breaching by invasive cancer cells. Noninvasive tumor cells do not degrade the BM (stage 0). Once cancer cells become invasive, invadopodia form and degrade the BM (stage 1). Further, invadopodia elongate (stage 2) and lead the cell to infiltrate into the stromal compartment (stage 3). (B) Cytoskeleton organization in invasive protrusions. Formation of invadopodia requires the assembly of dendritic and bundled actin networks (1a). Elongation of invadopodia is achieved by growth of actin bundles, which is sustained by the dendritic actin network (1b and 2a). Microtubules and intermediate filaments penetrate mature invadopodia while actin bundles are replaced by the expansion of the dendritic actin network (2b).