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

摘要

We report an extensive characterization of the Na⁺/monocarboxylate 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 polarized Madin–Darby canine kidney cells. We determine the kinetic parameters of SMCT activity and show its inhibition by ibuprofen (Ki = 73 ± 9 μM) in Xenopus laevis oocytes. SMCT was proposed to be a tumor suppressor in colon cancer [Li, H., et al. (2003) Proc. Natl. Acad. Sci. USA 100, 8412–8417]. Significantly, we show that higher expression of SMCT in colon samples from 113 colorectal cancer patients correlates with longer disease-free survival, suggesting that SMCT expression may be a favorable indicator of colorectal cancer prognosis.