期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 19, 页码 7270-7275出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0602365103
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资金
- NCI NIH HHS [CA098390, R01 CA098390] Funding Source: Medline
- NIDDK NIH HHS [R01 DK041544, DK41544] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007288, S06 GM053933-090006, S06 GM53933, S06 GM053933] Funding Source: Medline
- PHS HHS [T32 JM007288] Funding Source: Medline
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+/l(-) 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 (K-i = 73 +/- 9 mu M) 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.
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