Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance.
Yuji TakaokaMasamitsu KonnoJun KosekiHugh ColvinAyumu AsaiKeisuke TamariTaroh SatohMasaki MoriYuichiro DokiKazuhiko OgawaHideshi IshiiPublished in: Cancer science (2019)
Mitochondrial pyruvate carrier (MPC) is known to cause 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 siRNA or shRNA. We observed its cell morphology and accompanying molecular marker. Furthermore, the radioresistance of the 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 examination of the EMT marker by PCR showed 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.
Keyphrases
- epithelial mesenchymal transition
- induced apoptosis
- cell cycle arrest
- poor prognosis
- signaling pathway
- oxidative stress
- endoplasmic reticulum stress
- squamous cell carcinoma
- dna damage response
- binding protein
- endothelial cells
- mesenchymal stem cells
- pulmonary embolism
- cell therapy
- long non coding rna
- young adults
- high throughput
- pi k akt