Mechanisms of motility in metastasizing cells

Cell migration and invasion are critical parameters in the metastatic dissemination of cancer cells and the formation of metastasis, the major cause of death in cancer patients. Migratory cancer cells undergo dramatic molecular and cellular changes by remodeling their cell-cell and cell-matrix adhesion and their actin cytoskeleton, molecular processes that involve the activity of various signaling networks. Although in the past years, we have substantially expanded our knowledge on the cellular and molecular processes underlying cell migration and invasion in experimental systems, we still lack a clear understanding of how cancer cells disseminate in metastatic cancer patients. Different types of cancer cell migration seem to exist, including single-cell mesenchymal or amoeboid migration and collective cell migration. In most epithelial cancers, loss of the cell-cell adhesion molecule E-cadherin and gain of mesenchymal markers and promigratory signals underlie the conversion of epithelial, differentiated cells to mesenchymal, migratory, and invasive cells, a process referred to as the epithelial-to-mesenchymal transition. Although solitary migrating epithelial cancer cells have mostly undergone epithelial-to-mesenchymal transition (mesenchymal migration), and sometimes even lose their cell-matrix adhesion (amoeboid migration), collective migration of cancer cells in cell sheets, clusters, or streams is also frequently observed. The molecular mechanisms defining the different modes of cancer cell migration remain in most parts to be delineated.