Actin-based motile processes in tumor cell invasion

Tumor cell invasion and metastasis is a multi-step process where tumor cells escape from the primary tumor and seed at distant sites in the body. The invasion of tumor cells through the surrounding extracellular matrix (ECM) and intravasation through the endothelium to enter the bloodstream requires several highly regulated actin-based motile processes including: 1. Chemotaxis 2. Formation of invasive protrusions 3. Active cell migration, and 4. Active focal degradation of the ECM. The invasive tumor cell generates highly specialized actin-based invasive protrusions known as lamellipodia to initiate active cell migration and invadopodia to actively degrade through dense areas of ECM. The formation of both lamellipodia and invadopodia requires precise control of the activities of several proteins that function to regulate the actin cytoskeleton including: cortactin, cofilin, the Arp2/3 complex, diaphanous-related formins (DRFs), and myosin. In this chapter, we will discuss the molecular mechanisms that are known to control the actin cytoskeleton during the formation and maturation of both lamellipodia and invadopodia, and the contribution of these actin-based motile processes to the invasive tumor cell phenotype during metastasis in vivo.