To initiate this process, the Rho GTPase Cdc42, in its GTP-activated form, binds and activates N-WASP by inducing a conformational change that liberates the autoinhibited structure, thereby interacting with Arp2/3 complex, and regulating the protrusive formation in membrane structures promoting extracellular matrix (ECM) degradation. In cancer cells, when N-WASP interacts and activates the Arp2/3 complex, it catalyzes actin polymerization and assembly into filopodia and invadopodia. The WASP family proteins are key regulators of the actin cytoskeleton and cell migration through induction of membrane protrusions at the leading edge.
Unlike Ras, Rac and Cdc42 are not mutated in breast cancer, but activated via the deregulation of expression and/or activity of their upstream regulators, guanine nucleotide exchange factors (GEFs). The Rho GTPases, Rac, and Cdc42 are key molecular switches activated by a myriad of cell surface receptors to promote breast cancer cell migration/invasion, proliferation, and survival. In cell migration, the reorganization of the actin cytoskeleton produces the force necessary for cell migration. Invadopodia are actin-rich protrusive structures with associated matrix degradation activity and are believed to be important for tumor cells to penetrate the basement membrane of epithelia and blood vessels. Several proteins play a key role in this process, by the extension of structures known as invadopodia. Cancer cell invasion involves cell migration through the extracellular matrix (ECM) and the accompanying degradation of the ECM. If breast cancer is detected and treated prior to metastasis, the patient has a higher probability of being cured of their disease. In women, breast cancer is the leading cause of death, mainly due to metastasis.