Figure 2.

Steps of invadopodia formation. A. The invadopodia lifecycle can be divided in four steps: Initiation, assembly, maturation and disassembly. Cells begin to form invadopodia in response to activating signals transmitted by growth factor or matrix receptors, MMP activity, heterotypic cell interaction, EMT or oncogenic transformation. These signals activate different signaling pathways that induce branched actin polymerization and formation of a cellular protrusion. Once invadopodia are mature, different proteases are secreted, allowing degradation of the surrounding matrix. The final step consists in the dissolution of the invadopodia, which includes branched actin disassembly. B. Role of Cortactin in invadopodia disassembly. Invadopodia dissolution is triggered by the activation of Rac1 by its GEF Trio; in turn Rac1 activates PAK1, which is recruited by p27 on Cortactin. Then, PAK1 phosphorylates Cortactin on S113, S150 and/or S282, which probably induces the release of Cortactin from branched F-actin, destabilizing the branched actin network which disassembles, allowing the return to a basal situation.