2.A.1.13.6
Plasma membrane proton-linked monocarboxylate transporter, MCT4 or MCT-4 (SLC16A3). It catalyzes the rapid low affinity plasma membrane transport of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate.  It is the main transporter that catalyzes lactate efflux from glycolyzing cells (Halestrap 2013; Papakonstantinou et al. 2021).  Residues binding high affinity inhibitors have been identified (Nancolas et al. 2015).  Forms a complex with binding partner, CD147/BSG, which regulates the transport activity (Fisel et al. 2015). It plays a role in aggressive breast cancer subtypes (Li et al. 2018) as well as other cancers (Park et al. 2018).  MCT4 may be a therapeutic target for colorectal cancer (Kim et al. 2018). MCTs 1 and 4 are present in increased amounts in solid tumors, and inhibitors are potential therapeutics (Puri and Juvale 2020). Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT-4/lactate-mediated intracellular acidosis (Li et al. 2022). Dietary folate deficiency promotes lactate metabolic disorders that sensitize lung cancer metastasis through mTOR-signaling-mediated targets (Chen et al. 2023).