Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease

Abstract

Solute carrier (SLC) transporters represent 52 families of membrane transport proteins that function in endogenous compound homeostasis and xenobiotic disposition, and have been exploited in drug delivery and therapeutic targeting strategies. In particular, the SLC16 family that encodes for the 14 isoforms of the monocarboxylate transporter (MCT) family plays a significant role in the absorption, tissue distribution, and clearance of both endogenous and exogenous compounds. MCTs are required for the transport of essential cell nutrients and for cellular metabolic and pH regulation. Recent publications have indicated their novel roles in disease, and thus their potential as biomarkers and new therapeutic targets in disease are under investigation. More research into MCT isoform function, specificity, expression, and regulation will allow researchers to exploit the potential utility of MCTs in the clinic as therapeutic targets and prognostic factors of disease.

Figure 1

A scheme illustrating the lactate shuttling pathway in glycolytic and oxidative cancer cells. Glycolytic cancer cells (Left), dependent on glucose uptake via glucose transporters (GLUTs), undergo glycolysis to produce pyruvate and ATP, in which pyruvate undergoes further metabolism into lactate via lactate dehydrogenase A (LDHA). Proton symport-mediated lactate efflux occurs by MCT4. In oxidative cancer cells (Right), proton symport-mediated lactate influx and efflux occurs by MCT1. In these cells, lactate is transformed into pyruvate via lactate dehydrogenase B (LDHB) with the generation of NADH as a byproduct. These two metabolic products are then incorporated into the TCA cycle in mitochondria, to supplement the production of ATP via the oxidative phosphorylation pathway. This figure and caption was adapted from Perez-Escuredo et al.