Solute carrier family 16 member 3 (Monocarboxylate transporter 4) (SLC16A3)

Solute carrier family 16 member 3 (SLC16A3), commonly known as Monocarboxylate transporter 4 (MCT4), is a transmembrane protein that functions as a proton-coupled symporter, primarily facilitating the efflux of L-lactate and pyruvate from cells [1, 5, 9]. It is a member of the solute carrier family 16 and is predominantly expressed in highly glycolytic tissues, such as fast-twitch skeletal muscle and astrocytes, where it prevents intracellular acidification by exporting metabolic byproducts [1, 5, 6]. In oncology, SLC16A3 is frequently upregulated in various solid tumors, including lung, breast, and pancreatic cancers, supporting the "Warburg effect" by exporting excess lactate produced during rapid glycolysis [1, 4, 10]. This lactate export not only maintains a favorable intracellular pH for tumor survival but also acidifies the tumor microenvironment, which promotes immunosuppression, angiogenesis, and metastasis [4, 8, 10, 15]. Consequently, SLC16A3 has emerged as a significant therapeutic target and prognostic biomarker, with small-molecule inhibitors like AZD0095 and MSC-4381 under investigation to disrupt tumor metabolism and enhance the efficacy of treatments such as immune checkpoint inhibitors and EGFR-TKIs [10, 12, 16].

Other names

MCT4MCT 4MCT-4Monocarboxylate transporter 4Solute carrier family 16 member 3Monocarboxylic acid transporter 4

Inhibition of lactate efflux, induction of intracellular acidification, and metabolic stress induction.