An Adenosine-Mediated Signaling Pathway Suppresses Prenylation of the GTPase Rap1B and Promotes Cell Scattering

摘要: During metastasis, cancer cells acquire the ability to dissociate from each other and migrate, which is recapitulated in vitro as cell scattering. The small guanosine triphosphatase (GTPase) Rap1 opposes scattering by promoting cell-cell adhesion, a function that requires its prenylation, or posttranslational modification with carboxyl-terminal isoprenoid moiety, enable localization at membranes. Thus, signaling cascades regulate prenylation of offer mechanism control membrane Rap1. We identified cascade initiated adenosine A2B receptors suppressed Rap1B through phosphorylation Rap1B, decreased interaction chaperone protein SmgGDS (small GTPase diphosphate dissociation stimulator). These events promoted cytosolic nuclear accumulation nonprenylated diminished resulting found was more abundant mammary tumors than normal tissue rats activation delayed breast, lung, pancreatic lines. Our findings support model high concentrations extracellular adenosine, such those arise tumor microenvironment, can chronically activate suppress membrane, reduced contact Inhibiting may be an effective method prevent metastasis.