Role of the human Concentrative Nucleoside Transporter 1 (hCNT1) in oncogenesis

Abstract

Transportome alterations have been associated with oncogenesis. The loss of human Concentrative Nucleoside Transporter 1 (hCNT1) during carcinogenesis seems to be a relatively common event in tumors and might by itself contributing to oncogenesis. In fact, hCNT1 can play a dual role in cell biology being a nucleoside and nucleoside-derived drug transporter but also an important player in the modulation of a variety of cellular functions. Accordingly, we have previously reported that hCNT1 function is able to induce physiological changes that are relevant to tumor biology in a transport independent-manner. These observations argued in favor of hCNT1 being a transceptor protein. Thus, in this thesis we focused our study on the role of hCNT1 in cell physiology beyond the mere nucleoside salvage. We found that hCNT1 is able to induce antiproliferative effects in different tumor backgrounds, and its restitution in Hepatocellular carcinoma (HCC) derived cell lines alters several different signaling cascades that are important to many physiological functions of the cell, including cell survival and cell migration. Moreover, hCNT1-induced cell death seems to be triggered by an increase in intracellular Ca2+ levels, which might be related to the interaction of the Ca2+-binding protein S100A11 with hCNT1.