Role of MCT1 in cancer metabolism

Abstract

Many cancer cells exhibit an altered metabolism characterized by increased aerobic glycolysis known as the Warburg effect. To elucidate transcriptional events necessary for the Warburg effect in cancer, we compared gene expression profiles from glycolytic versus less glycolytic breast tumors and cancer cell lines. Amongst the mRNAs that significantly correlated with glycolytic phenotype was one encoding monocarboxylate transporter 1 (MCT1). MCT1 facilitates proton‐linked transport of lactate, pyruvate, and other monocarboxylates across the plasma membrane. We found that MCT1 levels are elevated in malignant breast lesions, and high MCT1 expression predicts poor prognosis in breast cancer patients. MCT1 LOF results in decreased glucose consumption rates in multiple breast cancer cell lines; however, MCT1 LOF does not consistently result in altered lactate production rates. Surprisingly, our data suggests that MCT1 primarily functions to export pyruvate, and that breast cancer cell lines export significant amounts of pyruvate. MCT1 LOF dramatically reduces breast cancer cell proliferation by causing a G1 cell cycle arrest, and reduces mammary fat pad tumor xenograft formation. Together, these data show MCT1 to be critical for breast cancer cell metabolism and proliferation, and suggest that MCT1 inhibitors may be effective anti‐cancer agents.