Rap1 promotes Prostate Cancer metastasis

Abstract

Elucidating the mechanisms of prostate cancer (CaP) survival and metastasis are critical to the discovery of novel therapeutic targets. Increasing evidence demonstrates significant roles for integrins and matrix metalloproteinases (MMP) in CaP metastasis, making them attractive targets for therapy. The monomeric G protein, Rap1 activates integrins and has been implicated in cancer tumorgenesis. Rap1 signals to pathways involved in cell adhesion, migration, and survival, suggesting Rap1 may promote several processes associated with CaP metastasis. Thus, we sought to explore the functional significance of Rap1 activation in CaP by examining its impact on invasion and migration of CaP cells during metastasis.Results from in vitro assays demonstrate activation of Rap1 increases CaP cell migration toward bone‐secreted factors. Similarly, results show activation of Rap1 enhances CaP cell invasion, and may involve modulation of MMPs. Inhibition studies indicate that integrin activation is a mechanism of Rap1‐mediated CaP migration and invasion. Additional studies will explore whether Rap1 influences MMPs directly or through its subsequent activation of integrins. The in vivo impact of Rap1 in CaP is being evaluated in the mouse and preliminary results demonstrate activated Rap1 drives the rate and incidence of CaP metastasis.Support for CLB: Department of Defense PCRP #DAMD17‐0510560