SLC16A4 Membrane Protein Introduction

Introduction of SLC16A4

SLC16A4 is encoded by the SLC16A4 gene and is also known as Monocarboxylate transporter 5 (MCT5), Monocarboxylate transporter 4 (MCT 4) and Solute carrier family 16 member 4. It belongs to the monocarboxylate transporter (MCT) family which consists of plasma membrane transporter proteins involved in the transport of lactic acid and other metabolic monocarboxylates. SLC16A4 possess 12 transmembrane alpha helices.

Function of SLC16A4 Membrane Protein

SLC16A4, a monocarboxylate transporter of lactate, pyruvate and other monocarboxylates, is the most significantly overexpressed gene in pseudomyxoma peritonei. SLC16A4 is expressed in the intestine and is a potential therapeutic target in conditions characterized by hypoxia. Highly elevated SLC16A4 expression appears to be pseudomyxoma peritonei specific, with equivalent elevated levels limited to only some colorectal tumors and cancer cell lines. Gallagher et al. reported that the specific interaction of SLC16A4 with β1 integrin may regulate cell migration and the specific interaction of SLC16A4 with β1-integrin may regulate cell migration through modulation of focal adhesions. SLC16A4 plays a multifaceted role in ARPE-19 cell migration because the expression of SLC16A4 at the leading edge could relieve the cell of the intracellular acid load, allowing glycolysis to continue uninterrupted. The efflux of lactate via SLC16A4 could serve to stabilize integrin-mediated attachment and modulate assembly/disassembly of focal adhesions at the leading edge, thereby enhancing directed cell migration. SLC16A4 plays an important role in cell migration, including PVR and metastatic cancer.

Fig.1 Proposed structure of SLC16A5 membrane protein. (Halestrap, 2013)

Application of SLC16A5 Membrane Protein in Literature

1. Biankin A.V., et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012, 491(7424):399-405. PubMed ID: 23103869
   
   

   This article reports that SLC16A4 is involved in chromatin modification, DNA damage repair, and other mechanisms. Meanwhile, integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for SLC16A4 genetic aberrations in carcinogenesis.

2. Roberts D.L., et al. Global gene expression in pseudomyxoma peritonei, with parallel development of two immortalized cell lines. Oncotarget. 2015, 6(13):10786-10800. PubMed ID: 25929336
   
   

   The results of this article indicate that SLC16A4 is expressed in the intestine and is a potential therapeutic target in conditions characterized by hypoxia.

3. Clatot F., et al. The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma. Oral Oncol. 2014, 50(3):200-207. PubMed ID: 24387976
   
   

   Authors in this group apply clustering analysis underlined the independent prognostic value of the expression of a panel of genes involved in hypoxia and tumor environment. A 9-gene model (VHL, PTGER4, HK1, SLC16A4, DLL4, CXCL12, CXCR4, PTGER3 and CA9) which can be applied routinely to classify newly diagnosed head and neck squamous cell carcinoma.

4. Choi H-D., et al. Analysis of gene expression during mineralization of cultured human periodontal ligament cells. Journal of Periodontal & Implant Science. 2011, 41(1):30-43. PubMed ID: 21394295
   
   

   The findings of this article suggest that related genes, including CXCL12, CCL8, SLC16A4, and ALDH1A3, were more strongly up-regulated during the early stage of mineralization or the late stage of matrix maturation by hPDL cells cultured in non-osteogenic medium were more associated with cell migration.

5. Beckner M.E., et al. Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1. BBA Clinical. 2016, 5:1-15. PubMed ID: 27051584
   
   

   Authors in this article used multiplex ligation-dependent probe amplification to reveal that monocarboxylate transporters (SLC16A3 or MCT4, SLC16A4 or MCT5) are important prognostic and therapeutic implications.

SLC16A4 Preparation Options

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Reference

1. Halestrap AP. (2013) The SLC16 gene family – Structure, role and regulation in health and disease. Molecular Aspects of Medicine. 34(2):337-349.

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