Monocarboxylate transporter 1 (MCT1) (MCT1)

Monocarboxylate transporter 1 (MCT1), encoded by the SLC16A1 gene, is a vital transmembrane protein that facilitates the proton-linked bidirectional transport of monocarboxylates, most notably L-lactate, across the plasma membrane (UniProt: P53347). While it can export lactate, its primary clinical significance in oncology is its role in L-lactate uptake, which fuels the oxidative metabolism of "metabolic symbiosis" in tumor cells (PubMed: 18948954). By importing lactate, MCT1 allows aerobic tumor cells to spare glucose for hypoxic cells, thereby promoting overall tumor growth and survival (PubMed: 22430211). Therapeutic targeting of MCT1, such as with the small molecule inhibitor AZD3965, aims to block this uptake, leading to intracellular acidification and metabolic exhaustion in cancer cells (NCT01791595). Beyond its role in cancer, MCT1 is crucial for the transport of ketone bodies in the brain and lactate in red blood cells and muscle tissue (PubMed: 10455110). Mutations in SLC16A1 are associated with hyperinsulinemic hypoglycemia and erythrocyte lactate transporter deficiency (NIH: GeneID 6566). Clinical challenges in targeting MCT1 include potential side effects such as retinal toxicity and muscle fatigue, as the transporter is expressed in the retina and is necessary for systemic lactate clearance during exercise (PubMed: 29037803).

Other names

SLC16A1Solute carrier family 16 member 1H(+)/monocarboxylate transporter 1Lactate transporter

Inhibition of L-lactate and proton symport across the plasma membrane, resulting in the disruption of pH homeostasis and the inhibition of lactate-fueled oxidative phosphorylation in tumor cells.