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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Na+/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: Molecular characterization of SMCT
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Na+/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: Molecular characterization of SMCT

机译：Na + /单羧酸盐转运（SMCT）蛋白表达与结肠癌的生存率相关：SMCT的分子特征

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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.
机译：我们报告的Na + /单羧酸盐转运蛋白（SMCT），介导单羧酸盐如丙酸盐和烟酸盐的主动运输的质膜蛋白的广泛表征，并且我们表明SMCT可能在结直肠癌的诊断中发挥作用。 SLC5A8基因的产物SMCT与Na + / l（-）转运蛋白（介导甲状腺细胞和其他细胞的基底外侧表面的活性I摄取）的蛋白质类似，为70％。据报道，SMCT在甲状腺细胞的根尖表面，以前也提出了转运I-的称呼，它被称为根尖I-转运蛋白。但是，现在很明显SMCT不会传输I-。在这里，我们证明了甲状腺细胞中高亲和力的Na +依赖性单羧酸盐转运系统，可能是SMCT。我们显示，虽然甲状腺Na + / I-转运蛋白表达是甲状腺刺激激素（TSH）依赖性和基底外侧，但SMCT表达是TSH依赖性的，并且不仅在甲状腺而且在肾脏和结肠上皮细胞以及极化的Madin中都呈顶端-杜比犬肾细胞。我们确定SMCT活性的动力学参数，并显示其在非洲爪蟾卵母细胞中被布洛芬（K-i = 73 +/- 9μM）抑制。有人提出将SMCT作为结肠癌的抑癌药[Li，H.，et al。 （2003年）过程。 Natl。学院科学USA 100，8412-8417]。重要的是，我们显示来自113位大肠癌患者的结肠样品中SMCT的较高表达与更长的无病生存期相关，这表明SMCT表达可能是结直肠癌预后的有利指标。

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