Molecular signaling mechanisms of cell migration and invasion.

The ability of immune cells to migrate and invade the extracellular matrix (ECM) is a central process involved in immunologic surveillance as well as inflammation. We have shown that interaction of cells with adhesive proteins or growth factors (chemokines) present in the ECM control cell migration/invasion through activation of mitogen-activated protein kinases ERK1 and ERK2 and molecular coupling of the adapter proteins p130CAS and c-CrkII. During cell migration, ERK and CAS/Crk coupling operate as distinct signaling pathways that facilitate actin-myosin motor assembly and actin membrane ruffles, respectively. Furthermore, activation of these signaling pathways protects cells from apoptosis during invasion of the ECM, which is necessary as migratory cells colonize foreign sites in the body.