Na ⁺ /monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: Molecular characterization of SMCT

Abstract

We report an extensive characterization of the Na ؉ ͞monocarboxy-late transporter (SMCT), a plasma membrane protein that mediates active transport of monocarboxylates such as propionate and nicotinate, and we show that SMCT may play a role in colorectal cancer diagnosis. SMCT, the product of the SLC5A8 gene, is 70% similar to the Na ؉ ͞I ؊ symporter, the protein that mediates active I ؊ uptake in the basolateral surface of thyrocytes and other cells. SMCT was reported in the apical surface of thyrocytes and formerly proposed also to transport I ؊ and was called the apical I ؊ transporter. However, it is now clear that SMCT does not transport I ؊ . Here we demonstrate a high-affinity Na ؉ -dependent monocarboxylate transport system in thyroid cells, which is likely to be SMCT. We show that, whereas thyroidal Na ؉ ͞I ؊ symporter expression is thyroid-stimulating hormone (TSH)-dependent and basolateral, SMCT expression is TSH-independent and apical not only in the thyroid but also in kidney and colon epithelial cells and in

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

“…The other is SLC5A8 (human apical iodide transporter, hAIT), which was suggested to charge the release of iodide into the colloid across the apical membrane as an iodide channel [29,30]. However, this gene was found to serve as a sodium monocarboxylate transporter and does not mediate iodide uptake or efflux [31]. The actual actions of the PDS gene remain to be clearly demonstrated; however, PDS is primarily thought to mediate iodide efflux from cells [32].…”

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

“…Thus, SLC5A8 was designated human Apical Iodide Transporter (hAIT). Later it was shown that SLC5A8 overexpressed in Xenopus laevis oocytes mediates the sodium-coupled transport of monocarboxylates like L-lactate, propionate, butyrate, or nicotinate, whereas exposure to iodide or bromate did not lead to currents (7)(8)(9). The sodium-dependent transport of monocarboxylates by SLC5A8 was also corroborated in a mammalian expression system (10) leading to renaming of the molecule as Sodium Monocarboxylate Transporter 1 (SMCT 1).…”

“…SLC5A8 methylation and transcriptional down-regulation has been linked to colon cancer susceptibility or to survival rates of colon cancer patients (9,15), and possible mechanisms for the tumor suppressive function have been suggested (32). Furthermore, there are reports on aberrant methylation of SLC5A8 in gastric cancer and on SLC5A8 silencing in papillary thyroid carcinomas (17) or glioma formation (18).…”

“…Similarly, re-expression of SLC5A8 in colon cancer cell lines lacking SLC5A8 suppressed colony growth (15). Potential tumor suppressive effects of SLC5A8 were also demonstrated for colon cancer (9), gastric cancer (16), thyroid cancer (17), and oligodendroglioma (18). It was claimed that SLC5A8-mediated transport of butyrate might serve as the molecular basis for the tumor suppressive role of SLC5A8 (19).…”

Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1

“…We focused on transmembrane proteins and successfully identified NaGLT1, which mediates the tubular reabsorption of glucose and fructose (11,13). In addition, this database includes a Slc5a8, which was characterized as a monocarboxylate transporter, and is thought to be a tumor suppressor (27,31). Moreover, mouse Oatp5 was also identified (3).…”