Solute carrier family 16 member 3 (MCT4) (MCT4)

Solute carrier family 16 member 3 (SLC16A3), which encodes the Monocarboxylate transporter 4 (MCT4) protein, is a critical mediator of metabolic homeostasis in glycolytic tissues (UniProt P53985). The primary biological function of the SLC16A3 product is the proton-coupled efflux of lactate from cells, a process essential for maintaining intracellular pH in cells with high rates of glycolysis (PubMed: 27992859). In oncology, SLC16A3 is frequently upregulated in response to hypoxia via HIF-1alpha, facilitating the Warburg effect and promoting tumor growth, invasion, and a pro-tumorigenic microenvironment (PubMed: 30554115). Targeting SLC16A3 mRNA through RNA interference or antisense oligonucleotides, or inhibiting the resulting MCT4 protein with small molecules like syrosingopine, disrupts lactate export and leads to intracellular acidification and metabolic exhaustion (PubMed: 29249690). This target is particularly relevant for aggressive, glycolytic cancers where it serves as a biomarker for poor prognosis and a potential therapeutic vulnerability (PubMed: 31431473).

Other names

Monocarboxylate transporter 4MCT 4SLC16A3Solute carrier family 16 member 3 mRNA

Inhibition of proton-coupled monocarboxylate transport, specifically lactate efflux, resulting in intracellular acidification and glycolytic inhibition.