Physiological and pharmacological roles of nucleoside transporter proteins.

Nucleoside transporter proteins, CNT and ENT, encoded by gene families SLC28 and SLC29, respectively, mediate the uptake of natural nucleosides (among them adenosine) and are major routes of entry for a variety of nucleoside analogs used in anticancer and antiviral therapies. Expression of NT proteins is apparently redundant in most cell types, and the elucidation of their particular physiological roles still remains elusive. Moreover, transporter-mediated uptake of nucleoside-derived anticancer drugs is crucial for the pharmacogenomic response triggered by these molecules in tumor cells. This review focuses on recent data demonstrating that nucleoside transporters, particularly CNTs, can play physiological roles other than salvage, whereas particular NT isoforms can significantly contribute to the transcriptomic response triggered by nucleoside analogs in cancer cells.