SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter
SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter
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DOI：
10.1016/j.lfs.2005.10.028
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发表时间：
2006-04-18
期刊：
影响因子：
6.1
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Gupta, N;Martin, PM;Ganapathy, V
SLC5A8作为肿瘤抑制基因在结直肠癌中的发现，首次标志着质膜转运蛋白与肿瘤抑制特性的关联。随后SLC5A8作为短链单羧酸的Na+偶联转运体的功能认同的建立为转运体的Turner抑制功能提供了一种机制。丁酸盐是转运蛋白的底物，是一种历史悠久的脱乙酰酶抑制剂，对结直肠癌具有保护作用。这种脂肪酸是通过饮食纤维的细菌发酵在结肠腔中产生的。SLC5A8介导丁酸从肠腔向结肠细胞的集中进入。因此，SLC5A8的转运功能能够影响病史的乙酰化状态，从而影响克隆细胞的基因表达。SLC5A8将丁酸输送到结肠上皮细胞的能力很可能是该转运蛋白的肿瘤抑制作用的基础。(C)2005 Elsevier Inc.保留所有权利。
The identification of SLC5A8 as a tumor suppressor gene in colorectal cancer marks, for the first time, the association of a plasma membrane transporter with tumor suppressive properties. The subsequent establishment of the functional identity of SLC5A8 as a Na+-coupled transporter for short-chain monocarboxylates provides a mechanism for the turner suppressive function of the transporter. Butyrate, a substrate for the transporter, is a historic deacetylase inhibitor and protective against colorectal cancer. This fatty acid is produced in the colonic lumen by bacterial fermentation of dietary fiber. SLC5A8 mediates the concentrative entry of butyrate from die lumen into colonocytes. Consequently, the transport function of SLC5A8 has the ability to influence the acetylation status of histories and hence gene expression in colonocytes. The ability of SLC5A8 to deliver butyrate into colonic epithelial cells most likely underlies the tumor suppressive role of this transporter. (c) 2005 Elsevier Inc. All rights reserved.