Gupta Naren, Martin Pamela M, Prasad Puttur D, Ganapathy Vadivel
Department of Biochemistry, Medical College of Georgia, Augusta, GA 30912, USA.
Life Sci. 2006 Apr 18;78(21):2419-25. doi: 10.1016/j.lfs.2005.10.028. Epub 2005 Dec 20.
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 tumor suppressive function of the transporter. Butyrate, a substrate for the transporter, is a histone 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 the lumen into colonocytes. Consequently, the transport function of SLC5A8 has the ability to influence the acetylation status of histones 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.
溶质载体家族5成员8（SLC5A8）作为结直肠癌中的一种肿瘤抑制基因被鉴定出来，这首次标志着一种质膜转运蛋白与肿瘤抑制特性之间的关联。随后确定了SLC5A8作为短链单羧酸的钠偶联转运蛋白的功能特性，这为该转运蛋白的肿瘤抑制功能提供了一种机制。丁酸盐是该转运蛋白的一种底物，它是一种组蛋白脱乙酰酶抑制剂，对结直肠癌具有保护作用。这种脂肪酸是由膳食纤维在结肠腔中通过细菌发酵产生的。SLC5A8介导丁酸盐从肠腔向结肠细胞的浓缩性内流。因此，SLC5A8的转运功能有能力影响组蛋白的乙酰化状态，进而影响结肠细胞中的基因表达。SLC5A8将丁酸盐输送到结肠上皮细胞的能力很可能是该转运蛋白发挥肿瘤抑制作用的基础。
