The Mechanism Of PPARα In Regulating Cancer Cell Glucose Metabolism

Tumor cell metabolism plays an important role in tumor development.Abundant nutrient availability(such as glucose and amino acids)is required for cancer cell energetic and biosynthetic pathways.Malignant cancer cells increase intake of nutrients by metabolic reprogramming(e.g.,increase the expression of Glut1).Peroxisome-proliferator-activated receptor α(PPARα)plays a critical role in the regulation of inflammation and cancer.However,it is still unclear the relationship between PPARα and cancer cell glucose metabolism.Our findings suggested that PPARα suppressed Glut1 gene transcription leading to inhibition of mTOR signaling pathways and tumor growth.The significant findings are as below: 1.PPARα decreased Glut1 gene and protein levels.2.PPARα shRNA silenced cells led to increased Glut1 gene and protein levels.3.Luciferase assay,ChIP analysis,EMSA results showed that PPARα inhibited Glut1 transcription activity by binding to Glut1 promoter region.4.Xenograft mice model showed that PPARα inhibited the expression of Glut1 gene,leading to inhibition of mTOR signaling pathways and tumor growth.5.PPARα agonists inhibited the expression of Glut1 and mTOR signaling pathways in tumor.6.PPARα agonist increased cancer cell sensitivity to chemotherapy drug,which was mediated by PPARα/Glut1 signaling pathways.