Adenosine promotes tumor metastasis.

An early step in tumor metastasis is a reduction in cell-cell adhesion to enable cell scattering. Contacts between cells are stabilized by accumulation in the plasma membrane of the small guanosine triphosphatase (GTPase) Rap1B. The membrane localization of Rap1B is increased when it is posttranslationally modified by prenylation of its C-terminal Cys-Ala-Ala-X motif. A new study shows that Rap1B prenylation and plasma membrane localization were reduced when Rap1B was phosphorylated by protein kinase A (PKA). In some tumors, high adenosine production and an abundance of G(s)-coupled adenosine A(2B) receptors would be expected to cause persistent PKA signaling and reduced Rap1B prenylation. These findings suggest that adenosine signaling reduces prenylation and plasma membrane localization of Rap1B, resulting in enhanced tumor cell scattering and invasiveness.