SLC16A3 Membrane Protein Introduction

Introduction of SLC16A3

SLC16A3 is encoded by the SLC16A3 gene and is also known as Monocarboxylate transporter 4 and Solute carrier family 16 member 3. It belongs to the MCT family, which is a transmembrane protein that facilitates the transport of short-chain carbohydrates such as pyruvate and lactate, with MCT1–SLC16A3 being preferentially involved in the transport of lactic acid. It is widely known that SLC16A3 transports lactate out of cells, which is very important for the acid-resistant phenotype of cancer cell.

Function of SLC16A3 Membrane Protein

SLC16A3 is responsible for the transport of lactic acid. The export of lactate by SLC16A3 prevents a decrease in cytosolic pH and inhibition of continued glycolysis. SLC16A3 is restricted to ‘‘glycolytic’’ tissues such as rapid-twitch skeletal muscle and astrocytes. Given its central role in controlling intracellular pH and lactate-based metabolism, SLC16A3 has been evaluated in various cancers, including cervical, colorectal, breast, melanoma, kidney and lung cancers. In general, the upregulation of SLC16A3 proteins is observed in tumor tissue and supports an apparent need for lactate shuttling to either fuel tumor growth or enable survival under stress conditions. The expression of lactate transporters in pancreatic ductal adenocarcinoma (PDA) and observed a striking upregulation of the SLC6A3 gene encoding SLC16A3. SLC16A3 expression was heterogeneous in PDA and associated with glycolytic metabolism and poor prognosis. SLC16A3 plays a key and intersecting role of multiple metabolic processes in specifying tumor cell survival.

Fig.1 Signaling pathway of SLC16A3 in glycolytic metabolism and poor prognosis pancreatic cancer. (Baek, 2014)

Application of SLC16A3 Membrane Protein in Literature

1. Baek G., et al. SLC16A3 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies. Cell Reports. 2014, 9(6):2233-2249. PubMed ID: 25497091
   
   

   This article reports that the lactate transporter SLC16A3 is a critical determinant of disease prognosis and glycolytic metabolism. Depletion of SLC16A3 induces compensatory metabolism to avert a metabolic crisis and targeting SLC16A3 suppresses tumor growth and yields vulnerability to metabolic stress.

2. Tan Z., et al. The Monocarboxylate Transporter 4 Is Required for Glycolytic Reprogramming and Inflammatory Response in Macrophages. The Journal of Biological Chemistry. 2015, 290(1):46-55. PubMed ID: 25406319
   
   

   This article reveals that SLC16A3 up-regulation represents a positive feedback mechanism in macrophages to maintain a high glycolytic rate that is essential to a fully activated inflammatory response.

3. Gao H-J., et al. Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration. J. Cancer Res. Clin. Oncol. 2015, 141(7):1151-1162. PubMed ID: 25446815
   
   

   This article suggests that SLC16A3 plays an important role in hepatocellular carcinoma cell proliferation, migration, and invasion because the inhibition of SLC16A3 can induce inactivation of HIF-1α and inhibit phosphorylation of AKT. So, SLC16A3 may be a potential therapeutic target for the treatment of hepatocellular carcinoma.

4. Zhu J., et al. Monocarboxylate Transporter 4 Facilitates Cell Proliferation and Migration and Is Associated with Poor Prognosis in Oral Squamous Cell Carcinoma Patients. PLoS ONE. 2014, 9(1):e87904. PubMed ID: 24498219
   
   

   This article shows that knock-down of SLC16A3 decreased cell proliferation, migration, and invasion. The findings of this article provide new insight into the critical role of SLC16A3 in cell proliferation and metastasis in oral squamous cell carcinoma.

5. Choi S.Y.C., et al. Targeting SLC16A3 to reduce lactic acid secretion and glycolysis for treatment of neuroendocrine prostate cancer. Cancer Medicine. 2018, 7(7):3385-3392. PubMed ID: 29905005
   
   

   The results of this article indicate that elevated glycolysis coupled to excessive SLC16A3 mediated lactic acid secretion is clinically relevant and functionally important to neuroendocrine prostate cancer. Inhibition of SLC16A3 expression appears to be a promising therapeutic strategy for neuroendocrine prostate cancer.

SLC16A3 Preparation Options

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Reference

1. Baek G., et al. (2014) SLC16A3 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies. Cell Reports. 9(6):2233-2249.

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