Monocarboxylate transporter 1 (MCT1), Monocarboxylate transporter 2 (MCT2), and Monocarboxylate transporter 4 (MCT4) (MCT1/2/4)

Monocarboxylate transporters 1, 2, and 4 (MCT1, MCT2, MCT4) are proton-linked plasma membrane transporters belonging to the SLC16 family (Halestrap, 2013). They facilitate the bidirectional transport of essential metabolites such as L-lactate, pyruvate, and ketone bodies, playing a critical role in cellular energy metabolism and pH homeostasis (Halestrap & Wilson, 2012). In many cancers, these transporters are upregulated to support the Warburg effect, enabling the efflux of glycolytic lactate via MCT4 and its uptake by oxidative cells via MCT1 (Doherty & Cleveland, 2013). This metabolic cooperation, known as metabolic symbiosis, promotes tumor growth, survival, and resistance to therapy (Sonveaux et al., 2008). Targeting these transporters, particularly MCT1 and MCT4, has emerged as a promising strategy in oncology to disrupt tumor metabolism and induce intracellular acidification (Beloueche-Babari et al., 2017). However, therapeutic development faces challenges such as on-target toxicities in the retina and heart, where MCT1 is physiologically expressed, and the potential for compensatory resistance mechanisms (Halford et al., 2017).

Other names

SLC16A1SLC16A7SLC16A3Solute carrier family 16 member 1Solute carrier family 16 member 7Solute carrier family 16 member 3H+/monocarboxylate symportersLactate transportersProton-coupled monocarboxylate transporters

Inhibition of proton-coupled monocarboxylate transport, leading to intracellular acidification and disruption of metabolic symbiosis.