Schematic model of the general mechanism of exocytosis of MT1-MMP–positive late endosomes at the invadopodial plasma membrane. WASH-dependent Arp2/3 complex activation and actin/cortactin assembly controls the dynamics of tubular endosomal membrane extensions (inset i) and tubular endosome-to-plasma connections required for transfer and delivery of MT1-MMP from the endosome to the invadopodial plasma membrane (inset ii). The exocyst complex mediates tethering of MT1-MMP–positive late endosomes with the target membrane (ii). Fusion between the endosomal membrane tubule and the invadopodial plasma membrane may necessitate the SNARE protein VAMP7 (not depicted; Steffen et al., 2008; Williams and Coppolino, 2011). Actin and cortactin assembly at invadopodia requires N-WASP and allows membrane protrusion formation and retention of MT1-MMP (insets ii and iii; Yamaguchi et al., 2005; Artym et al., 2006; Oser et al., 2010; Yu et al., 2012). Mature invadopodia are responsible for penetrating and breaching the basement membrane in contact with carcinoma cells (1 and 2; Hotary et al., 2006; Rowe and Weiss, 2008). In the fibrous, collagen-rich extracellular membrane environment surrounding the tumor (3), fibers that oppose cell movement, involving recognition by yet unidentified collagen receptors, trigger the assembly of N-WASP– and F-actin–positive linear invadopodia and the recruitment and exocytosis of MT1-MMP–containing endosomes based on the conserved WASH and exocyst-dependent mechanism (inset iv).