Mitochondrial pyruvate carrier 1 expression controls cancer EMT and radioresistance

Summary

Mitochondrial pyruvate carrier (MPC) is known to bring about different expressions in normal and cancer cells. We observed a change in phenotype with the suppression of MPC expression. We knocked down MPC1 and/or MPC2 using small interfering RNA or short hairpin RNA. We observed its cell morphology and accompanying molecular marker. Furthermore, the radioresistance of MPC knockdown cell line was examined using a colony formation assay. MPC1 suppressed cells changed their morphology to a spindle shape. Epithelial‐mesenchymal transition (EMT) was suspected, and the examination of the EMT marker by polymerase chain reaction revealed a decrease in E‐cadherin and an increase in fibronectin. Focusing on glutamine metabolism as the mechanism of this phenomenon, we knocked down the glutamine‐metabolizing enzyme glutaminase (GLS). EMT was also observed in GLS suppressed cells. Furthermore, when MPC1 suppressed cells were cultured in a glutamine‐deficient medium, changes in EMT markers were suppressed. In addition, MPC1 suppressed cells also increased with a significant difference in radioresistance. Decreased MPC1 expression favorably affects EMT and radioresistance of cancer.

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