Rap1 as a potential drug target in tissue colonization of invasive leukemia tumor cells

Abstract

The actin skeleton is involved in many morphological cell processes, like cell shape, cell and extracellular matrix adhesion and migration. For this, the actin skeleton is interacting with the outside of the cell using focal adhesions, adherens and tight junctions. These interactions are build up by specialized molecules, such as family members of the integrins. The formation of the actin skeleton and transmembrane junctions are regulated by the small GTPase Rap1. Moreover, Rap1 was described to be so important for these processes that in several cell lines knockdown of Rap1 totally inhibited migration. Especially Rap1 deficiency in the high motile immune cells, this can lead to severe diseases. Based on other literature findings, we state that overactivation of Rap1 is also inhibiting migration of cells. Since leukemias generally arise in immune cells we further investigated the role of Rap1 in this disease. If Rap1 is so important for cell migration, it is very plausible that inhibiting or overactivating Rap1 activity in leukemias specifically could inhibit cancer metastasis. This could make Rap1 a good drug target in leukemia and maybe also in other cancers. Here, we review the possibility of using Rap1GEFs and Rap1GAPs as potential drugs or drug targets to alter Rap1 activity.