SLC5A8 Membrane Protein Introduction

Introduction of SLC5A8

SLC5A8 is encoded by SLC5A8 gene. It belongs to the solute carrier family 5 which has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. It is a sodium-coupled transporter for monocarboxylates, such as lactate, pyruvate, acetate, propionate, and butyrate. SLC5A8 is regarded as a putative tumor suppressor in colon. It is usually expressed on the luminal surface of colonic epithelial cells, which indicates it may play an important role in transporting bacterial metabolite into colonic epithelial cells.

Function of SLC5A8 Membrane Protein

SLC5A8, also named as sodium-coupled monocarboxylate transporter 1 (SMCT1), is expressed in various tissues, such as small bowel, stomach, brain, thyroid, lung, and kidney. Its substrates are the HDAC (histone deacetylase) inhibitors butyrate, propionate, and pyruvate. Expression of SLC5A8 is silenced in cancers via DNA methylation, and ectopic expression of SLC5A8 in cancer cells induces apoptosis in the presence of its substrates that are HDAC inhibitors. Recent studies have indicated that the silence of SLC5A8 is involved with a wide variety of cancers, including cancers of brain, colon, thyroid, pancreas, prostate, lung and breast. In addition, studies conducted on SLC5A8 indicate that SLC5A8 nuclear translocation and loss of expression are associated with poor outcome in pancreatic ductal adenocarcinoma.

Fig.1 A cell with SLC and non-SLC transporters expressions. (Sharma, 2013)

Application of SLC5A8 Membrane Protein in Literature

1. Sivaprakasam S., et al. Short-chain fatty acid transporters: Role in colonic homeostasis. Compr Physiol. 2017, 8(1): 299-314. PubMed ID: 29357130
   
   

   This article examines the expression level of several transport systems include SMCT1 and SMCT2 in ulcerative colitis and colon cancer. They also identify the potential mechanisms of tumor-associated changes in these transport systems. The results suggest that there are differences in the expression of these transporters.

2. López-Barradas A., et al. Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1 (SMCT1/SLC5A8). Am J Physiol Cell Physiol. 2016, 311(5), C720-C734. PubMed ID: 27488665
   
   

   This article analyzes the role of insulin in human SMCT1 xenopus oocytes. The data indicate that human SMCT1 is regulated by insulin and SGK1 and that both SMCTs are present in the mammalian pancreas.

3. Orellana-Manzano A., et al. Helicobacter pylori infection is associated with decreased expression of SLC5A8, a cancer suppressor gene, in young children. Front Cell Infect Microbiol. 2016, 6: 121. PubMed ID: 27777899
   
   

   Authors in this group conduct a case-control study to examine the expression of SLC5A8 in blood samples collected from H. pylori-infected and non-infected children. The data illustrate that H. pylori infection is associated with suppression of SCL5A8 in all samples from children.

4. Hu B.S., et al. Downregulation of SLC5A8 inhibits hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling. Tumour Biol. 2016, 37(10): 13445-13453. PubMed ID: 27465549
   
   

   This article examines the expression level of SLC5A8 in hepatocellular carcinoma (HCC) and tries to identify the biological functions of SLC5A8 in HCC. The results show that patients with a low SLC5A8 expression have a shorter overall survival time, and overexpression of SLC5A8 can suppress HCC cell growth.

5. Zane M., et al. Circulating cell-free DNA, SLC5A8, and SLC26A4 hypermethylation, BRAF(V600E): A non-invasive tool panel for early detection of thyroid cancer. Biomed Pharmacother. 2013, 67(8): 723-30. PubMed ID: 23931930
   
   

   This article analyzes the cf-DNA expression and methylation of SLC5A8 and SLC26A4, BRAF(V600E) mutation in various cancer patients. The data demonstrate that cf-DNA shows a high ability in cancer patients and these genes could be targets for thyroid cancer diagnosis.

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Reference

1. Hediger M A, et al. (2013). The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 34(2-3), 95-107.

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