Roles of Rap1 signaling in tumor cell migration and invasion.

Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein family, is an important regulator of basic cellularfunctions (e.g., formation and control of cell adhesions and junctions), cellular migration, and polarization. Through itsinteraction with other proteins, Rap1 plays many roles during cell invasion and metastasis in different cancers. The basic functionof Rap1 is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosinetriphosphate (GTP) or guanosine diphosphate (GDP). However, its remarkably diverse function is rendered by its interplay with alarge number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizesthe mechanisms by which Rap1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherinregulation, Rho GTPase control, and matrix metalloproteinase expression.