Invadopodia: the leading force.

Metastatic spread of cancer cells is the leading cause of mortality from cancer. Metastatic cancer cells must penetrate through several barriers to escape the primary tumor and gain entry into the bloodstream in order to spread to other tissues. It is believed that invasive cancer cells penetrate these barriers by forming specialized F-actin rich protrusions called invadopodia that localize matrix degrading activity to cell-substrate contact points. Invadopodia gain their protrusive ability by combining the physical force generated by actin polymerization with the chemical activity of matrix degradation. Accumulating data over the past few years have shed light on the molecular mechanisms as well as kinase signaling pathways that regulate the complex process of actin polymerization in invadopodia. Here we review some of these mechanisms, the signaling pathways that regulate this process, as well as the in vivo relevance of invadopodial structures. Understanding the mechanisms that govern invadopodia formation and function is an essential step in the prevention of cancer invasion and metastasis.